No retraction, correction or concern found when last checked on Oct 19, 2026.

A Comprehensive Review of Autophagy and Its Various Roles in Infectious, Non-Infectious, and Lifestyle Diseases: Current Knowledge and Prospects for Disease Prevention, Novel Drug Design, and Therapy

Rekha Khandia, Maryam Dadar, Ashok Munjal and 8 more

Cells · 2019 · Review · CC BY

Abstract

Autophagy (self-eating) is a conserved cellular degradation process that plays important roles in maintaining homeostasis and preventing nutritional, metabolic, and infection-mediated stresses. Autophagy dysfunction can have various pathological consequences, including tumor progression, pathogen hyper-virulence, and neurodegeneration. This review describes the mechanisms of autophagy and its associations with other cell death mechanisms, including apoptosis, necrosis, necroptosis, and autosis. Autophagy has both positive and negative roles in infection, cancer, neural development, metabolism, cardiovascular health, immunity, and iron homeostasis. Genetic defects in autophagy can have pathological consequences, such as static childhood encephalopathy with neurodegeneration in adulthood, Crohn’s disease, hereditary spastic paraparesis, Danon disease, X-linked myopathy with excessive autophagy, and sporadic inclusion body myositis. Further studies on the process of autophagy in different microbial infections could help to design and develop novel therapeutic strategies against important pathogenic microbes. This review on the progress and prospects of autophagy research describes various activators and suppressors, which could be used to design novel intervention strategies against numerous diseases and develop therapeutic drugs to protect human and animal health.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 19, 2026. Paragraph numbers are ours, so an answer can point at one.

1. Introduction

1Autophagy is a conserved catabolic process that is involved in cellular homeostasis and is required to maintain normal cellular physiology under stressful conditions. It overcomes carcinogenic, infectious, degenerative, and deleterious agents to maintain the homeostasis of bodily systems and regulate healthy life processes; thus, its dysregulation is known to cause multiple human diseases. Autophagy can be a selective or non-selective lysosomal degradative process and is activated by stresses such as starvation or rapamycin via regulatory signaling complexes. There are three types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). Macroautophagy, referred to as “autophagy” from now on, is the major pathway which engulfs large portions of cytoplasm and cellular contents (e.g., long-lived proteins, aggregated proteins, damaged organelles, and intracellular pathogens) into a double-membraned vacuole called the autophagosome, which fuses with lysosomes to form an autolysosome, degrades the autolysosomal contents, and recycles macromolecules for reuse.

2Microautophagy refers to the process by which lysosomes directly engulf and digest small volumes of cytosolic substrate, whilst CMA is induced by physiological stresses such as prolonged starvation and involves the heat shock cognate protein (HSC70; 71-kDa, also known as HSPA8) which contains a KFERQ-like pentapeptide sequence. The CMA pathway delivers target proteins across lysosomal membranes into the lysosomal lumen by interacting with lysosome-associated membrane protein type 2A (LAMP-2A). Hence, CMA differs from microautophagy and macroautophagy, as it does not require vesicular trafficking. Regardless of the type, autophagy acts as a cleaning mechanism by removing or degrading unnecessary materials from the body (e.g., proteins, organelles, and microbes) and retaining or maintaining materials (biochemicals, metabolites, and organelles) required for survival, function, and development. The physiological processes of autophagy are governed by numerous cellular regulators (e.g., transcription factors and genes), which can affect homeostatic processing if disturbed by genetic or functional reasons, or overexertion. Hence, autophagy defects can affect the pathogenesis of many diseases.

3The roles of autophagy have been explored in fields such as health, disease, infection, degeneration, and genetic or lifestyle-acquired diseases; however, cancer, microbial infections, and degenerative diseases have been the main focus of autophagy-related research. Currently, the roles of autophagy are being explored in diverse fields of study.

4Autophagy plays important roles in cancer metastasis; 4-acetyl-antroquinonol B has been shown to modulate autophagy and prevent the growth of ovarian cancer cells. Clinical studies have revealed higher levels of autophagic flux in distant metastases than in primary tumors; therefore, autophagy has stage-dependent dual roles in cancer which may facilitate the growth and spread of tumors and affect treatment resistance. Conversely, autophagy has been shown to act as a tumor suppressor during the early and late phases of cancer development by mediating the destruction and removal of carcinogens and cancerous cells, thus enabling the growth and development of healthy cells; however, under disturbed or uncontrolled conditions autophagy can promote cancer growth and dissemination. Autophagy is also important in neuronal homeostasis, with its dysfunction associated with numerous neurodegenerative disorders. Pathogenic protein aggregates are a common feature of neurodegenerative disorders, and dysfunctional autophagy is involved in this disease state. Furthermore, mutations in autophagy regulation genes have been shown to induce neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer’s disease, and familial Parkinson’s disease. These mutations affect different stages of autophagy and thus have different implications for pathogenesis and therapy.

5In the modern world, factors such as globalization, liberal trade, climate change, population explosions, public health lapses, immune pressures, and mutations, species jumping, and emerging antibiotic resistance in pathogens have facilitated the spread of various infectious pathogens. In recent years, it has been shown that autophagy has a role in many emerging and re-emerging infectious viral and bacterial diseases that pose significant threats to humans. Autophagy initially encounters these infectious pathogens to neutralize them; however, may infections can propagate themselves as persistent intracellular infections and are generally associated with wide outbreaks, epidemics, and highly devastating effects. Many viral life cycles are linked with autophagic pathways. The influenza A virus induces autophagosome formation during the early stages of infection and inhibits autophagosomal maturation during the later stages. Classical swine fever virus replication is negatively regulated by mTORC1 via autophagy and IRES-dependent translation, whilst Dengue/Zika virus pathogenicity is modulated by antibody-dependent enhancement (ADE) which can induce autophagy in human umbilical vein endothelial cells. Multimodal necrotic cell death is driven by open reading frame-3a of severe acute respiratory syndrome (SARS)-coronavirus (CoV), that triggers the lysosomal damage and dysfunction and therefore transcription of autophagy-related genes is enhanced, whilst endoplasmic reticulum (ER) stress in Dengue virus (DENV) infections results in autophagy activation, viral replication, and pathogenesis. The disruption of mitochondrial membrane potentials by the non-structural protein of Crimean-Congo hemorrhagic fever (CCHF) virus results in apoptosis, whereas paramyxovirus V proteins inhibit constitutively active MDA5 proteins to induce autophagy. All of these viral events are related to autophagy and can provide directions for future therapies for Chikungunya (CHIKV), DENV, and Zika virus (ZIKV) infections. Autophagy has a pivotal role in viral diseases such as bird flu, swine fever, Ebola virus disease, ZIKV infection, SARS, CHIKV infection, DENV infection, viral encephalitis, CCHF, Hendra virus (HeV) infection, Nipah virus (NiV) infection, and the West Nile virus (WNV) infection. Apart from these, other viral diseases, such as rabies, rotavirus enteritis, and smallpox, have already posed a serious threat to human life. Autophagy has also been shown to have a central role in microbial infections, including those caused by Listeria, Salmonella, Shigella, and Streptococcus. Autophagy can kill or eradicate infectious disease-causing pathogens via the autophagosome or autophagolysosome (autolysosome) to prevent or treat infection; however, autophagy can also disseminate pathogens during pathogenesis. For example, gut epithelial autophagy can disseminate viruses and bacteria in enteric diseases. Therefore, autophagy can play a dual role in infections.

6In recent years, there has been an increase in the incidence of lifestyle and genetic diseases, such as cancers and neurodegenerative disorders (Alzheimer’s, Parkinson’s, and Huntington’s diseases), which affect the quality of life. Advances in science and technology have contributed to overcoming these challenges. Novel, alternative, and complementary therapeutic options have been developed, including phages, homing peptides, cytokines, siRNA, viral inhibitors, Toll-like receptors (TLRs), antibodies, probiotics, herbs, phytomedicines, nanomedicines, and immunomodulatory techniques. Autophagy is the first mechanism to clear endogenous debris and exogenous substances and maintains normal physiological conditions in all eukaryotic cells. Besides maintaining homeostasis, autophagy also regulates the development, differentiation, and maturation of cells, such as endothelial cells, erythrocytes, and adipocytes. These cells are involved in normal physiological (e.g., erythrocytes in respiration), immunological (e.g., mononuclear cells in immunity), metabolic (e.g., adipocytes in fat metabolism), growth (e.g., osteocytes in bone growth), and development (e.g., spermatozoa or ova in reproduction) processes. Autophagy is also involved in clearing abnormal protein accumulations and correcting mitochondrial disorganization. The processes of autophagy and apoptosis are interwoven and have been implicated in both microbial infections and cancers. Autophagy might play both physiological and pathological roles since it is involved in overcoming cell stresses. Considering the numerous roles and functions of autophagy in health and disease, we present a comprehensive overview of autophagy, its mechanisms and types, and its associations with other cell death mechanisms. The dual roles of autophagy in infectious diseases (bacterial and viral), tumor suppression/progression, brain development/neurodegeneration, the immune system, and autoimmune diseases, and its other roles have been discussed thoroughly alongside numerous applications of autophagy. We have also summarized the role of autophagy in cardiovascular diseases, iron homeostasis, obesity, diabetes, and diseases caused by defects in autophagy genes. The treatment of autophagy-associated diseases has been described alongside strategies to inhibit or activate autophagy in the prevention and treatment of diseases. This review details the important functions of autophagy in health and disease and its key roles in disease prevention and treatment.

2. Autophagy: A Brief Overview

7Autophagy (from the Greek words auto, meaning self, and phagy, meaning eating), is an essential, ubiquitous, evolutionarily conserved, catabolic, and self-degradative process that mediates the destruction of cytoplasmic macromolecules to preserve genomic integrity, achieve cell metabolism, and ensure cell survival. It is a natural regulatory mechanism which retains beneficial substances and removes harmful substances from body, whilst playing a housekeeping role in the elimination of misfolded or aggregated proteins, the eradication of damaged organelles, proteins, and cancerous materials, and the elimination of foreign pathogens such as viruses via a degradative lysosomal pathway.

8Numerous physiobiological roles of autophagy have been identified, such as the disposal of endogenous wastes and exogenous agents to maintain homeostasis; however, disturbing the natural balance of this mechanism can result in pathological consequences.

9Since it is the primary system for cleaning the body, autophagy can prevent or treat cancer by killing cancerous cells and degrading endogenous or exogenous carcinogens; thus, favoring the development of healthy cells. However, autophagy may have dual roles in cancer as it is involved in stem cell-related resistance to anti-cancer therapy (radioresistance and chemoresistance), metastasis, and tumor recurrence. As obligate intracellular pathogens, viruses interact with multiple host cell processes for their survival, including metabolism, cellular trafficking, and immunity-related responses. Furthermore, autophagy is a major degradative cellular process, with essential roles in many innate and adaptive immune processes. Autophagy also regulates the phosphorylation of p38 and ERK1/2 MAPKs in BV2 microglial cells, required for nitric oxide production. Thus, it can affect the activation of neuronal cells by microglia and suppress neurotoxicity. Moreover, it can downregulate pro-inflammatory mediators in BV2 microglial cells to rescue them from LPS- and α-synuclein-induced neuronal cell death.

10Autophagy can either be selective or non-selective. In selective autophagy, cargo is recognized by specific receptors to enable their specific identification, sequestration, and degradation by the autophagosome, whereas in non-specific autophagy, all materials are degraded by the lysosome in a non-specific manner. Furthermore, autophagy is known to exist in two forms: constitutive and reactive (induced) autophagy. Constitutive autophagy has not been well studied, whereas the latter has been studied extensively and is known to stimulate neurite remodeling in developing brains, thus may be essential during brain development. Mice lacking the autophagy proteins Atg59 and Atg710 display excessive neurodegeneration, indicating that autophagy has physiological importance. Numerous factors relating to nutrient deprivation (amino acids and hormones) and build-up of degraded products (proteins) or exogenous agents (pathogens) have been evaluated as induced autophagy stimuli. Endogenous and exogenous stimuli induce autophagy for degradation or as a repair mechanism.

11Several stimuli have been shown to induce autophagy, including stress, amino acid starvation, rapid declines in trophic factors or hormones (such as sex-based differences), lipid starvation, impaired intracellular cholesterol trafficking, protein products, and infectious pathogens. These stimuli can affect the autophagic function and induce different morphological consequences via diverse signaling pathways; for instance, suppressing phosphatidylinositol-3-kinase (PI3K) inhibitors and Beclin 1 inhibits the starvation-induced mitochondrial autophagy, but not the neurotoxin (1-methyl-4-phenylpyridinium)-mediated autophagy. Although autophagy was discovered over 50 years ago, its molecular mechanisms were only understood in the late 1990s following a genetic screening in yeast, which revealed mutations in autophagy-related genes. At least 30 yeast autophagy genes (Atgs) have been identified, many of which have mammalian cell homologs.

12Many molecular mechanisms have been explored to reveal the basic processes underlying autophagy. Multiple signaling pathways focus on two protein complexes to initiate autophagy, the ULK1 (unc51-like autophagy activating kinase 1) protein kinase complex and the PI3KC3-C1 (class III phosphatidylinositol 3-kinase complex I) lipid kinase complex. Novel autophagy regulators with RNA-related activities have also been shown to be involved in this process. Furthermore, upstream signaling pathways common to both autophagy and apoptosis are known to be induced by ER stress via signaling molecules such as PERK/ATF4, IRE1α, ATF6, and Ca2+. The details of these mechanisms will shed light on the different forms of autophagy and the numerous intermediates involved.

13Three types of autophagy [macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA)] are depicted in Figure 1.

2.1. Mechanisms of Autophagy

14Autophagy refers to the process of delivering cytoplasmic or extracellular components to the lysosomes of an animal cell or the vacuoles of plant or yeast cells. The production and maturation of autophagosomes are directly regulated by location, timing, and intensity. The phosphoinositide-binding protein, HS1BP3, is a negative regulator of autophagosome biogenesis that regulates the lipid composition and phosphatidic acid (PA) levels of autophagosome precursor membranes. Increased levels of systemic autophagy have been reported in Caenorhabditis elegans, with hormetic heat stress and heat-shock responsive transcription factor (HSF-1) inducing autophagy to improve the survival and proteostasis of the worm. Furthermore, it has been revealed that autophagy is fine-tuned by epigenetic regulation, through histone (coactivator-associated) arginine methyltransferase, CARM1, a novel enzyme that follows histone H3R17 dimethylation (histone H3 methylated at arginine 17) which is an important epigenetic marker of starvation-induced autophagy. In addition, the vitamin D receptor has been shown to modulate autophagy in normal mammary glands and luminal breast cancer cells, suggesting a potential therapeutic link between vitamin D levels and breast cancer risk. There are numerous additional endogenous and exogenous factors that modulate autophagy, such as transcription factors, variation in the amount or concentration of various cytoplasmic biochemicals, damaged organelles, exogenous compounds, and pathogens; therefore, autophagy mechanisms vary. Autophagy can be divided into macroautophagy, microautophagy, and CMA based on the mechanism by which intracellular materials are delivered into the lysosome for degradation and the molecular structures that target substrates to the lysosomes. Although these pathways are mechanistically distinct, they all carry out degradation via the lysosome. Most forms of selective autophagy involve the degradation of specific targets; for example, mitophagy (mitochondria), pexophagy (peroxisomes), aggrephagy (protein aggregates), glycophagy (glycogens), lipophagy (lipids), ribophagy (ribosome), xenophagy (pathogens), and ER-phagy. Autophagy is a novel, evolutionarily conserved function of the eukaryotic initiation factor 2 (eIF2α) kinase pathway, which consists of a family of evolutionarily conserved serine/threonine kinases that regulate stress-induced translational arrest and are targeted by virulence gene products.

2.1.1. Macroautophagy

15Macroautophagy is initiated when a portion of cytoplasm containing a cellular organelle is sequestered to form the autophagosome. The autophagosome fuses with the lysosome or late endosomal multivesicular bodies (MVBs) to degrade the materials within it. Atg8 (microtubule-associated protein 1A/1B-light chain 3, LC3, is an Atg8 homolog in humans) was the first autophagosomal protein to be characterized. Macroautophagy can be classified as cargo-specific or non-selective.

16Mitophagy has been observed in yeasts when a shift occurs between non-fermentable and fermentable carbon sources, such as glucose, following which the surplus mitochondrial population undergoes mitophagy. The first protein identified to cause mitophagy in yeast was Uth1p, a member of the SUN family, which is present in the outer mitochondrial membrane and allows excessive mitochondria to be removed during starvation. The mitochondrial outer membrane protein, Atg32, is a receptor for selective autophagy that is not conserved in mammalian species; instead, FUNDC1 and BNIP3, BNIP3L/NIX, and SQSTM1/p62 act as mitophagy receptors, and are dependent upon hypoxia, erythrocyte maturation, and damage-induced mitophagy, respectively. Pexophagy is also induced in Saccharomyces cerevisiae and Pichia pastoris via the Atg36 and PpAtg30 receptors, respectively, when the fungal medium is switched from an oleic acid or methanol to a glucose or nitrogen starvation medium. Starvation has also been shown to induce non-selective macroautophagy, whereas mitochondrial phospholipids have been demonstrated to be required for autophagy. The machinery required for selective autophagy has been studied extensively using yeast cells, revealing that the cytoplasm-to-vacuole targeting (CVT) pathway is used to specifically transport vacuolar hydrolases into the vacuole of budding yeast cells. A high degree of curvature in the initiating membranes (phagophores or isolation membranes) is a prominent feature of CVT vesicles during mammalian autophagy.

2.1.2. Microautophagy

17After the lysosome has formed vesicles by invaginating and engulfing small sections of the cytoplasm, lysosomal proteases degrade the contents of these vesicles. Microautophagy occurs during the biogenesis of multi-vesicular bodies (MVBs), which deliver soluble proteins to the late endosomes, and relies on electrostatic interactions between endosomal sorting complexes required for transport (ESCRT) I and III and the heat-shock cognate protein 70 (HSC70). Hence, microautophagy involves both endocytic and autophagic components.

2.1.3. Chaperone-Mediated Autophagy (CMA)

18Only proteins with a C-terminal pentapeptide KFERQ motif undergo CMA; the HSC70 cochaperone identifies cytosolic proteins containing this sequence and delivers them to the lysosome. Chaperones bound to the substrate are transported to the lysosomal surface, where they interact with the monomeric LAMP-2A. LAMP-2A must form a multiprotein complex to translocate the substrate; LAMP-2A complex assembly is a dynamic process that occurs when the substrate binds to the receptor. The unfolded substrate protein (chaperon-mediated) is then translocated into the lysosome by LAMP-2A for degradation, following which LAMP-2A disassembles and its monomers are degraded in lipid microdomains. The levels of LAMP-2A tightly regulate the rate of CMA at the lysosomal membrane. In the mammalian anti-viral defense system, a cell-autonomous autophagy mechanism has been identified wherein cellular p62 adaptor-mediated autophagic viral protein clearance induces cell survival. Some positive-strand RNA viruses, including picornaviruses and influenza virus, promote autophagic membrane formation, and inhibit their final maturation (lysosomal fusion). Consequently, studying the interactions between autophagy and adenoviruses could improve adenoviral-based oncolytic virotherapies. The process of CMA is depicted in Figure 2.

2.2. Molecular Mechanisms of Autophagy

19Autophagy is an evolutionarily conserved process induced via multiple signaling pathways by numerous stimuli including nutrient starvation, hypoxia, oxidative stress, pathogen infection, and ER stress. In the presence of nutritional substances and cytokines, mechanistic/mammalian target of rapamycin (mTOR) can prevent apoptosis and stimulate cell growth, whereas stress and nutrient starvation inhibit mTOR to initiate autophagy via at least four molecular complexes, including the unc-51-like kinase (ULK) complex, consisting of ULK-1, Atg13, Atg101, and FAK-family interacting protein (FIP200); the PI3K complex, consisting of Atg15, vacuolar protein sorting (VPS)15, VPS34, Beclin 1, and Beclin 1-regulated autophagy protein 1 (AMBRA1); transmembrane protein complexes, including Atg9 and WIPI; and two ubiquitin-like protein conjugation systems (Atg12 and LC3).

20Autophagy is initiated by the assembly of the ULK complex, which phosphorylates AMBRA1 and leads to activation of the PI3K complex. Class III PI3K is known to participate in various membrane trafficking events, whilst PI3K and Beclin 1 mediate membrane nucleation. The Atg5-Atg12-Atg16 complex is recruited to the pre-autophagosomal structure (PAS) where it associates with the outer membrane of the phagophore, essentially preventing the premature fusion of vesicles and lysosomes. The second ubiquitin-like system stimulates the binding of phosphatidylethanolamine (PE) and Atg8/microtubule-associated protein 1 light chain 3 (LC3). LC3 has a high affinity for the lysosome when bound to the phagosome (LAPosome); thus, any engulfed pathogens will be killed and degraded at a higher rate. Atg4, Atg7, and Atg3 process LC3 into LC3-II, a molecular marker for autophagosomes that is present on both its inner and outer surfaces and is essential for the expansion and completion of the autophagic membrane. Following autophagosomal closure, the Atg5-Atg12-Atg16 complex dissociates from the autophagosome. Atg9 is required for the formation of intraluminal vesicles and is localized within the autolysosome for acidification; Atg9 is also translocated to the site of autophagosome formation where it provides a membrane to elongate the limiting membrane, known as the phagophore. The autophagosome then fuses to the lysosome to form the autolysosome, which is regulated by lysosomal membrane proteins and cytoskeletal proteins. The LAMP-1/2 protein controls autophagosomal maturation. Genetic mutations in LAMP-2 are known to cause Danon disease, a glycogen storage disorder linked to hypertrophic cardiomyopathy, skeletal muscle weakness, and intellectual disability. Within the autolysosome, hydrolytic enzymes digest the internalized cargo and the internal autophagosome membrane, then the digested products such as amino acids are released into the cytosol to be recycled. Autophagosomes are also directly related to cell trafficking pathways.

21Recently, Holland et al. identified that the phosphoinositide-binding protein HS1BP3 negatively regulates autophagosome production. HS1BP3 is thought to reduce phospholipase D1 (PLD1) activity and its localization to ATG16L1 and transferrin receptor (TFRC)-positive vesicles. It is also known to regulate the levels of PA and the lipid content of autophagosome precursor membranes. Two large families of E3 ubiquitin ligases, TRIM and CULLIN, have been recognized as important autophagy regulators which promote or inhibit the process, respectively. The GTPase Ras-related protein in brain 7 (Rab7) also plays a key role in autophagy regulation, particularly in modulating its flux. Knockdown of the small GTPase Rab13 has been shown to inhibit pterostilbene-induced autophagy in vascular endothelial cells (VECs), whilst its upregulation stimulates autophagy in VECs. Under basal autophagy conditions in humans, proteomic analysis of the autophagy interaction network (AIN) revealed a network of 751 interactions between 409 candidate proteins. In order to identify the proteins modulating starvation-induced autophagy, genome-wide screening of siRNA in a GFP-LC3-expressing human cell line was carried out, shortlisting nine proteins. One of these, short coiled-coil protein (SCOC), forms an essential starvation-sensitive trimeric complex with UV radiation resistance-associated gene (UVRAG) and WAC (WW domain-containing adapter protein with coiled-coil), which is a negative regulator of the ubiquitin-proteasome system. Genome-wide studies in C. elegans identified 139 genes that promote autophagy when inactivated. Long ncRNAs (lncRNAs), which are longer than 200 nucleotides and do not encode proteins, often possess regulatory functions; for example, miR188-3 has been found to regulate Atg7 expression. RNA-linked strategies have revealed several autophagy regulators such as RNA-binding proteins (RBPs), which are post-transcriptional and co-translational regulators with RNA-related functions. Surprisingly, various key autophagy proteins, including LC3B and LAMP-2C, have been found to bind RNA. A considerable amount of autophagy research is being carried out worldwide; however, these innovative findings have raised numerous additional questions. To some extent, autophagy research has been protein-centric, and innovative new approaches have been developed to strengthen this focus in recent years. Among these, genome-wide screens and proteomics-based strategies have revealed substantial interlinking between autophagy and RNAs; however, the precise mechanisms underlying this association require further investigation. Future studies must develop and evaluate novel agents that specifically target the autophagy pathway.

22A pictorial representation of the process of autophagosome formation is presented in Figure 3.

2.3. Autosis: A Novel Form of Autophagy

23Liu and Levine described a novel form of non-apoptotic autophagic gene-dependent cell death, termed autosis, which is mediated by the Na+/K+-ATPase pump. Autosis involves enhanced cell-substrate adhesion, focal ballooning of the perinuclear space, and dilation and fragmentation of the endoplasmic reticulum. The Tat-Beclin 1 peptide complex may initiate autosis, with the fusion of the evolutionarily conserved, 18-amino acid-long Beclin 1 domain with 11 amino acids from the HIV Tat protein transduction domain aiding the cellular entry of the fusion peptide. The Tat-Beclin 1 fusion peptide has been shown to inhibit the replication of HIV, CHIKV, Sindbis (SINV), and WNV, as well as intracellular bacteria such as Listeria monocytogenes. Tat-Beclin 1 treatment also reduced mortality in neonatal mice infected with CHIKV and WNV, demonstrated using a TUNEL assay, and cleared mutant Huntingtin protein aggregates. Autosis can be partially rescued by knocking down Atg13 or Atg14 or using 3-methyladenine. Under serum/amino acid starvation, approximately 1% of dying cells exhibit a morphology similar to that of cells treated with Tat-Beclin 1 and autosis is selectively blocked when the Na+/K+-ATPase pump is inhibited. During cerebral hypoxia or ischemia, the neonatal brain releases cardiac glycosides (ouabain or endobain), which inhibit the Na+/K+-ATPase pump and reduce autosis. Autosis has also been observed in patients with severe liver anorexia nervosa who display focal ballooning of the perinuclear space, convoluted nucleus, dilated and fragmented ER, empty vacuoles, and several autolysosomes in their hepatocytes. Ischemic injury can also lead to autosis in other organs, including the kidney and heart, which is attenuated in Beclin 1+/− mice.

2.4. Association between Autophagy and Other Cell Death Mechanisms

24Autophagy can promote or inhibit cell death depending on the cellular context; many other death mechanisms are intricately involved in the processes, with several mechanistic links elucidated between autophagy and other death mechanisms.

2.4.1. Links between Autophagy and Apoptosis

25Autophagy and apoptosis regulation overlap when the BH3 domain of the Beclin 1 autophagy protein interacts with anti-apoptotic proteins of the Bcl-2 family, including Bcl-2, Bcl-xL, and Mcl-1. The BH3 domain has a critical role in the interaction between these proteins and has been shown to interact with the receptor domain of the Bcl-2 family in nutrient-rich cells. Beclin 1-mediated autophagy is inhibited by ER-localized Bcl-2; the transgenic expression of Bcl-2 was shown to inhibit autophagy in mouse heart muscles. Beclin 1 mutants, which are unable to bind to Bcl-2, induce higher levels of autophagy than their wild-type counterparts; hence the physical Beclin 1-Bcl-xL/Bcl-2 interaction regulates Beclin 1-mediated autophagy. ABT737, a compound which mimics the BH3 domain and thus inhibits this interaction, increases the aggregation of LC3, an autophagy marker which is present on autophagosomes, in both nutrient-rich and nutrient-deprived media. Furthermore, the knockdown of Beclin 1 and other essential Atg proteins using siRNA heteroduplexes was shown to reduce ABT737-stimulated LC3 aggregation. Atg12 is a dual-functioning protein that participates in both autophagy and apoptosis; non-conjugated Atg12 can bind and inhibit Mcl-1 and Bcl-2 via a BH3-like domain to positively regulate mitochondrial apoptosis. Atg12 knockout inhibits the release of cytochrome c from the mitochondria and apoptosis, whilst abnormal Atg12 expression represses the anti-apoptotic activity of Mcl-1.

26Autophagy promotes apoptosis by degrading a negative regulator of the Fas ligand; however, it can also protect cells against apoptosis induced by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) by altering the concentrations of Bcl family members. Similarly, components were found to be degraded by autophagy during developmental apoptosis, whilst it was recently shown that inhibiting autophagy increased apoptosis and accelerated mortality in murine sepsis models with inadequate autophagy pathways in CD4+ T cells, indicating that autophagy has a functional role against apoptosis and immunosuppression in T cells in sepsis. Furthermore, TRAIL combined with a novel chalcone derivative, Chal-24, was found to remarkably increase lung cancer cell cytotoxicity via autophagy-mediated apoptosis.

2.4.2. Autophagy and Necroptosis

27Necroptosis is often associated with inflammation. The relationship between autophagy and necroptosis is complex, elusive, and slightly controversial since reports have indicated that necroptosis may promote, inhibit, or do not affect autophagy. In several cell lines, including L929 cells, lymphocytes, and cancer cells, autophagy is activated in the presence of TNFα and under starvation to suppress necroptosis. The apoptosis-inhibiting peptide, carbobenzoxy-Val-Ala-Asp (zVAD), prevents autophagy and induces necroptosis in response to TNFα by regulating lysosomal cathepsins, highlighting the pro-survival function of autophagy against necroptosis. Similarly, inhibiting the mTOR signaling pathway can prevent apoptosis and even enhance necroptosis, whereas starvation, which induces autophagy, protects cells from zVAD-mediated necroptotic death.

28Sirtuins (SIRT) are NAD+-dependent protein deacetylases which are actively involved in both autophagy and necroptosis, as well as transcription, stress resistance, and aging. SIRT-1 deacetylates various components of the autophagy pathway, including Atg5, Atg7, and Atg8, thus promoting autophagy. In cancer cells, dissociation of the FoxO1 transcription factor from SIRT-2 during oxidative stress or starvation results in the acetylation and binding of FoxO1 to Atg7, which subsequently induces autophagy. The binding of SIRT-2 to receptor-interacting protein (RIP) 3 mediates RIP1 deacetylation in response to TNFα; RIP1 and RIP3 then form a complex, which triggers necroptosis. The switch between necroptosis and apoptosis is achieved by recruiting necrosome components to autophagy machinery. Atg5 knockdown reduced the association between RIPK1 and MLKL, suggesting that Atg5 is important in TRAIL-induced necrosome activation. Furthermore, Atg5 knockout in the Atg5-/- DF-1 cell line inhibited autophagy but promoted apoptosis. Autophagy machinery also affects the mechanism of cell death by promoting efficient necrosomal activation and MLKL phosphorylation, thus inducing necroptosis. Several anti-cancer agents, including sorafenib, cause deficient autophagosome formation and facilitate the interaction between p62 and RIPK, resulting in cell death by necroptosis; however, there is still much to be elucidated about the interplay between these two processes.

2.4.3. Autophagy and Necrosis

29Necrosis refers to the increase in cell volume caused by organelle swelling, which results in plasma membrane rupture and the loss of intracellular contents. When ATP is depleted, the cell is unable to undergo apoptosis and undergoes necrosis instead. Poly ADP ribose polymerase (PARP1) is an enzyme with roles in DNA repair, transcriptional regulation, and chromatin modification. PARP1 over-activation decreases the ATP reservoir and induces necrotic cell death by bypassing energy-dependent apoptotic cell death. ATP depletion also activates AMP-activated kinases (AMPK), which induce autophagy by activating the ULK1 complex or inhibiting mTOR signaling. Thus, DNA damage-induced PARP1 activation leads to a decline in ATP levels, AMPK activation, mTOR inhibition, and autophagy induction. PARP1 plays a dual role in autophagy and necrosis since autophagy is a pro-survival mechanism, whilst necrosis is a pro-death mechanism. The fate of the cell depends on the balance between autophagy and necrosis, where autophagy represents the final attempt of the cell to survive before necrosis.

3.1.1. Anti-Bacterial Role of Autophagy

30Autophagy plays a beneficial role against infectious diseases by simultaneously degrading pathogens and activating the host immune system. This enables infections to be countered directly, by killing infectious agents, and indirectly, by inducing host immunity against pathogens. Autophagy provides an excellent intracellular defense system against bacterial pathogens, including Salmonella enterica serovar Typhimurium, Listeria monocytogenes, and Shigella flexneri. Anti-bacterial autophagy is termed xenophagy. Numerous cellular, membrane-associated, or cytoplasmic moieties modulate xenophagy; and those cells unable to carry out xenophagy, exhibit higher rates of infection. Bcl-xL regulates xenophagy, and Bcl-xL knockout cells are more susceptible to Streptococcus pyogenes infection. The infection of non-phagocytic cells by Shigella flexneri is dependent upon type-III secretion system (T3SS) effector proteins which reorganize the host cell cytoskeleton, ruffle the cell membrane, and cause bacterial uptake. Following internalization, bacterial peptidoglycans are detected by nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) which trigger a pro-inflammatory immune response (Figure 4). The bacteria-sensing NOD proteins interact with Atg16L1 to initiate anti-bacterial autophagosome biogenesis in response to bacterial invasion. Intracellular bacterial sensing either by NLRs or sequestosome-1-like receptors (SLRs) recruits autophagy proteins, including unc-51-like kinase (ULK) 1/2 and lipid kinase complexed with Beclin 1 and Atg16L1, to initiate phagophore membrane nucleation and engulf invading bacteria.

31Mutant C. elegans with defective autophagy genes exhibit increased susceptibility to bacterial infection. In addition, it has been reported that HLH-30/TFEB-mediated autophagy and autophagy pathways can regulate the tolerance of C. elegans to Bacillus thuringiensis infection by protecting against its pore-forming toxins, suggesting a novel association between intrinsic epithelial defenses and HLH-30-mediated autophagy against in vivo bacterial attacks. Liang et al. reported that Beclin 1 overexpression inhibits Sindbis virus replication, indicating that autophagy protects against infectious pathogens. Autophagy may activate innate immunity against mycobacteria via pattern recognition receptors (PRRs) or non-receptor-mediated processes.

32Infection with group A Streptococcus species (GAS; Streptococcus pyogenes) induces anti-apoptotic Bcl-xL expression which inhibits autophagy directly by suppressing autophagosome-lysosome fusion, and indirectly by interacting with Beclin 1-UVRAG to suppress GAS internalization. In addition, Mycobacterium tuberculosis is known to induce miR144 expression in human macrophages and monocytes and adversely affect their antimicrobial activities and innate host immune responses against the bacterial infection by targeting DRAM2 (DNA damage-regulated autophagy modulator 2), which is a critical element of the autophagy response. The ubiquitin ligase, SMURF1, has also been shown to control M. tuberculosis replication in human macrophages by associating with bacteria in the lungs of patients with pulmonary tuberculosis. The murine macrophage cell line, RAW264.7, has been used to study Bacillus amyloliquefaciens SC06-induced autophagy and its anti-bacterial response against Escherichia coli; B. amyloliquefaciens stimulated autophagy by increasing the expression of Beclin 1 and the Atg5-Atg12-Atg16 complex, but not activating the AKT/mTOR signaling pathway.

33Several autophagy-inducing drugs have been used to treat microbial infections; for example, AR-12 [2-amino-N-[4-[5-(2 phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] phenyl]-acetamide] inhibits phosphoinositide-dependent kinase-1 and eliminates Salmonella typhimurium in murine macrophages and Francisella tularensis in human leukemic THP-1 macrophages. Furthermore, 1α,25-dihydroxycholecalciferol, a form of vitamin D, can enhance autophagy and inhibit human immunodeficiency virus (HIV) replication in macrophages.

34Many bacteria have evolved mechanisms to overcome autophagy and allow them to replicate within infected cells or even within autophagosomes. These bacteria may express receptors to prevent or enhance phagosome formation, capture nutrient containing phagosomes, subvert autophagy machinery, prevent fusion, or resist autophagy. Certain bacteria hijack autophagosomes and use the by-products of autophagic degradation for microbial replication. Anaplasma (formerly Ehrlichia) phagocytophilum, the causative agent of human anaplasmosis, uses the effector Anaplasma translocated substrate 1 (Ats-1) to enhance autophagosome formation and acquire nutrients from inside the autophagosome. After entering the cell, A. phagocytophilum replicates inside a double-lipid bilayer membrane associated with LC3 (Atg8), Beclin 1, and Atg6 but lacking lysosomal markers. Inhibiting autophagy with 3-methyladenine did not prevent bacterial internalization but arrested its growth, indicating that the autophagic machinery had been subverted to facilitate bacterial proliferation. Another bacterium, Yersinia pseudotuberculosis, replicates intracellularly inside specific compartments called Yersinia-containing vacuoles (YCVs), which contain autophagy markers; however, YCVs are not acidified and sustain bacterial replication. During Y. pestis infection, LC3-I is conjugated with PE to recruit LC3-II, a marker of autophagy progression, to the phagosomal membrane. A similar mechanism is used by Coxiella burnetii, the causative organism of Q fever. Coxiella-replicative vacuoles contain LC3, Beclin 1, and Rab24; overexpression of these proteins increases the number of Coxiella-replicative vacuoles. Brucella abortus replicates within Brucella-containing vacuoles (BCVs) which traffic from the endocytic compartment to the endoplasmic reticulum, where the bacteria proliferate. Bacterial proliferation requires the autophagy-initiation proteins ULK1, Beclin 1, and Atg14L; however, Atg5, Atg16L1, Atg4B, Atg7, and LC3B are not required.

35Pathogens such as Brucella spp. and Porphyromonas gingivalis have evolved to survive inside autophagosomes by preventing its fusion with the lysosome, thus escaping host innate immunity mechanisms. Salmonella typhimurium studies have revealed that autophagy targets invading intracellular bacterial pathogens for degradation; S. typhimurium regulates the SIRT1/LKB1/AMPK complex of the mTOR pathway by targeting SIRT1, LKB1, and AMPK to lysosomes for rapid degradation, restricting autophagy and disrupting AMPK-mediated mTOR regulation.

36Autophagy is differentially regulated in tuberculoid and lepromatous leprosy; in tuberculoid skin lesion cells, autophagy controls Mycobacterium leprae, whereas in lepromatous cells, the blocking of Bcl-2-mediated autophagy promotes bacterial persistence. IFN-γ may counteract the M. leprae–mediated inhibition of autophagy in lepromatous macrophages as autophagy levels were restored in lepromatous patients who developed the reversal reaction, an inflammatory state associated with augmented IFN-γ and rapamycin treatment, indicating that autophagy is an important innate mechanism associated with M. leprae control in skin macrophages.

3.1.2. Anti-Viral Role of Autophagy

37Autophagy has a beneficial role in cellular defense against invasion by viruses; therefore, it has been used for antiviral immunity. Autophagy helps to clear viral pathogens during infection via various molecular mechanisms, regulates immune responses, and prevents harmful overactivation and inflammation. For example, autophagy increases the presentation of endogenous viral antigens in the peptide grooves of major histocompatibility complex (MHC) class I molecules on the cell surface during herpes simplex virus type 1 (HSV-1) infection. Studies of viral peptides have suggested a complex interaction between vacuoles and MHC class I presentation pathways in autophagosomes. In contrast, MHC class II molecules continuously accept input from autophagosomes, which facilitates antigen presentation by MHC class II molecules. Autophagy is a major component of Drosophila immunity against vesicular stomatitis virus (VSV) as it can deliver viral antigens to TLRs for presentation. During anti-viral signaling, pattern recognition receptors (PRRs) at the plasma membrane (i.e., Toll-7) that are engaged by VSV stimulate an autophagy-dependent innate immune response mediated by PI3K-Akt-signaling. Furthermore, Toll/TLR signaling has been shown to regulate the Rift Valley fever virus (RVFV) replication in both flies and mammals, whilst SIRT1, an NAD(+)-dependent deacetylase, modulates the activation of dendritic cells and autophagy during induced immune responses against respiratory syncytial virus (RSV), thereby directing an effective anti-viral immune response. Furthermore, autophagy is stimulated by the salicylamide derivatives against cytopathic bovine viral diarrhea virus (cp-BVDV), a Flaviviridae pestivirus. Foot-and-mouth disease virus (FMDV) infection suppresses autophagy and NF-κB anti-viral activities by degrading Atg5-Atg12 using the viral protein, 3Cpro, suggesting that Atg5-Atg12 positively modulates anti-viral NF-κB and IRF3 pathways during FMDV infection to limit FMDV proliferation. However, autophagy is often hijacked by viral pathogens and can be modulated to their own benefit.

3.1.3. Proviral Role of Autophagy

38Subverting the autophagic pathway can have adverse consequences by giving pathogens access to nutrients for growth and reproduction. Autophagy plays an important role in viral replication and pathogenesis, with coronaviruses, coxsackievirus B3, poliovirus, hepatitis C virus (HCV), and DENV all known to stimulate and require autophagy for accelerated replication. For instance, autophagy has been demonstrated to be actively involved in the replication of influenza A virus (IAV), which induces autophagosome formation during the early phase of infection and later inhibits autophagosomal maturation by preventing autophagosomal-lysosomal fusion and promoting autophagosomes to accumulate in virus-infected cells. Autophagy-deficient cells are more susceptible to apoptosis upon influenza infection, while using pharmacological reagents or RNA interference to alter cellular autophagy can impair viral protein accumulation. Human single-chain antibody variable fragments (ScFvs) which bind to the influenza A virus ion channel protein (M2) and inhibit viral replication were found to restore autophagosome maturation suppressed by the infecting virus (personal communication). It has also been reported that HCV can trigger autophagy via immunity-related GTPase M, which promotes HCV replication. Paramyxoviruses such as Newcastle disease virus (NDV) have been shown to trigger autophagy in U251 glioma cells to enhance viral replication. In addition, modulating NDV-induced autophagy using rapamycin, chloroquine, or small interfering RNAs which target genes critical for autophagosome formation (Atg5 and Beclin 1) affects virus production, suggesting that NDV may utilize autophagy to promote its replication. Human immunodeficiency virus (HIV) uses multiple methods to regulate autophagy and enhance its replication. HIV induces the early stages of autophagy but inhibits the later stages which would suppress the production of new virions. The HIV-1 accessory protein, Nef, inhibits autophagosomal maturation by interacting with Beclin 1, whilst the HIV protein Vpr can trigger autophagy in transfected THP-1 macrophages, indicating that autophagy may be involved in maintaining HIV reservoirs in macrophages. HSV-1, Kaposi’s sarcoma-associated herpesvirus (KSHV), and mouse herpesvirus 68 (MHV-68) encode proteins that bind Beclin 1 to prevent autophagy initiation.

39During poliovirus (PV) infection, vesicle acidification, which can mature autophagosomes, has been shown to induce the maturation of virions into infectious particles. One of the most important characteristics of high-risk human papillomavirus (hrHPV) etiopathogenesis is that inhibiting host autophagy could cause cervical cancer via hrHPV. In epithelial cells, flavivirus NS4A-induced autophagy protects infected cells and induces viral replication. Autophagy also plays a critical role in the replication of coronaviruses and the generation of their replicative structures. Coronavirus nonstructural proteins (nsp6) induce the formation of omegasomes and autophagosomes from the ER via an omegasome intermediate. In addition, autophagy has been shown to induce the replication of infectious spleen and kidney necrosis virus (ISKNV) in the Chinese Perch Brain (CPB) cell line, suggesting complex interactions between ISKNV and host cells during viral pathogenesis and for anti-viral treatment strategies.

40Treating FMDV-infected cells with rapamycin, an autophagy inducer, was shown to increase viral replication, whilst inhibiting the autophagosomal pathway using 3-methyladenine or small-interfering RNAs decreased viral replication. Furthermore, disrupting autophagy using the knockdown approach in hepatitis C virus (HCV)-infected hepatocytes stimulated the interferon signaling pathway and induced apoptosis, indicating that HCV-induced autophagy can impair the innate immune response. Suppressing HCV-induced autophagy could be a promising approach for inhibiting exosome-mediated viral transmission, besides autophagy has been shown to reduce HCV clearance following IFN-α/Ribavirin (RBV)-based anti-viral therapy. A DENV study revealed that autophagy inhibitors are better candidate targets than conventional anti-viral therapies using interferons (IFNs); upregulating cellular autophagy was reported to inhibit RLR-mediated type-I IFN-independent signaling and cause the antibody-dependent enhancement (ADE) of DENV. Suppressing autophagic vacuoles has been demonstrated to stimulate the maturation of infectious bursal disease virus. Adenoviral infection may be favored by autophagy via an increase in ATP, essential to increase anabolism of the infected cells and amino acid pools for the synthesis of viral proteins. In the later stages of adenoviral infection, Atg12-Atg5 complex is significantly upregulated as an evidence of enhanced autophagy; therefore, autophagy may improve the virulence of some viruses. Autophagy genes are involved in the regulation and execution of autophagy. Beclin 1 was the first mammalian gene identified to stimulate autophagy. Some viruses, such as α-, β- and γ-herpesviruses, encode the neurovirulence protein, ICP34.5, which associates with Atg6/Beclin 1 and inhibits autophagy by preventing the formation of the PI3 kinase complex. The autophagy genes Fip200, Beclin 1, Atg14, Atg16l1, Atg7, Atg3, and Atg5 have been found to promote the reactivation of latent murine gamma-herpesvirus 68 by inhibiting virus-induced systemic inflammation molecules, such as IFN-γ. In contrast, autophagy inhibition has been reported as a new molecular mechanism by which HSV-1 escapes innate immunity, resulting in fatal disease. The autophagic cell death of alveolar epithelial cells has been observed to play a major role in the high mortality rate caused by H5N1 influenza virus infection; hence autophagy-blocking agents could have preventative and therapeutic effects against this virus. Activating the PI3K /Akt/mTOR pathway and inhibiting autophagy have been shown to promote the cellular entry of HPV type 16, contrarily autophagy has been shown to be essential for the replication of coronavirus and mouse hepatitis virus (MHV). HSV-1 mutants, those are unable to inhibit autophagy grows to low virus titer and are less pathogenic. Autophagy evokes antiviral adaptive immunity via the endogenous presentation of viral antigens through the MHC class II pathway.

41The proviral and anti-viral actions of autophagy are illustrated in Figure 5.

3.2. Autophagy in Tumor Suppression

42Initially, autophagy was thought to be involved in tumor suppression by stimulating gene expression, inhibiting proinflammatory mediators, inhibiting inflammation or inflammatory products, and stimulating signaling pathways. The essential Atg6/Beclin 1 gene was found to be lost monoallelically in 40–75 % of human prostate, breast, and ovarian cancers, whereas excessive autophagy stimulation by Beclin 1 overexpression has been reported to inhibit tumor progression. Autophagy causes necrosis and chronic inflammation by inhibiting the release of pro-inflammatory HMGB1, which is involved in tumorigenesis. In cell-based assays, inhibiting autophagy was shown to enhance cancer cell growth. p62 (a signaling adaptor/scaffold protein) is involved in the formation of intracellular ubiquitin-related protein aggregates because of autophagy deficiency. Atg7-deficient mice exhibit enhanced accumulation of p62 and ubiquitinated protein aggregates in hepatocytes and neuron. Autophagy has also been implicated in benign hepatomas, and the inactivation of Beclin 1 and Atg5 was shown to increase the incidence of cancer in mice. Atg5- and Atg7-deficient mice exhibited liver tumors, indicating that defective autophagy can affect the suppression of tumorigenesis. Heterozygous Beclin 1 (beclin 1+/- mutant) was shown to have a high incidence of spontaneous tumors, whilst Beclin 1 inhibited tumor growth in cell lines such as the breast cancer cell line, MCF-7, in which Beclin 1 expression was lower than in normal epithelial breast cells. The UVRAG protein was found to suppress the tumorigenicity and proliferation of human colonic cancer cells (Figure 6).

43Autophagy suppresses tumor formation by preventing inflammation, the accumulation of proteins and organelles damaged by necrosis, and cellular transformation caused by gene instability. The conserved protein kinase, mTOR, has been implicated in cancer since its substrates (eukaryotic initiation factor 4E (eIF4E)-binding proteins (4E-BPs) and ribosomal S6 kinases (S6Ks) 1 and 2) promote cell cycle progression. mTOR, which is inhibited by rapamycin, and molecules such as phosphatase and tensin homolog (PTEN) and tuberous sclerosis (TSC) (products of tumor suppressor genes) can induce autophagy. Pogostone, a medicinal herb widely used to treat gastrointestinal diseases, was shown to possess anti-colorectal tumor activities by stimulating autophagy and apoptosis via the PI3K/Akt/mTOR axis. In addition, the novel anti-cancer molecule HA15, which targets HSPA5/BIP, was shown to induce ER stress and increase the unfolded protein response, resulting in cancer cell death via autophagy and apoptosis. Trichosanthin (TCS), a 27 kDa protein from the bioactive component of the root tuber of Trichosanthes kirilowii (Chinese cucumber plant; Gua Lou in Mandarin), also exhibited anti-cancer properties against different human ovarian cancer cells via a pathway common to both autophagy and apoptosis.

3.3. Autophagy in Tumor Progression

44Various factors and mechanisms are involved in autophagy-mediated tumor progression. Tumor-induced nutrient shortage, cell debris (degraded proteins), inflammation, and oxidative cascades are all molecular mechanisms affecting tumor progression. During nutrient starvation, autophagy induction promotes the survival of normal cells and may also promote tumor cell survival; however, hypoxia, metabolic stress, energy shortage, oxidative stress-damaged mitochondria, and organelles can be caused by cancer-causing genes or cancer treatments. The undifferentiated colon cancer cell line, HT-29, and other transformed cells have shown an increased tendency to degrade autophagic proteins. The elevated expression of the autophagy signature protein, BNIP3, a pro-apoptotic Bcl-2 member, has been demonstrated in colorectal and gastric epithelial carcinomas, suggesting that BNIP3 expression may be important for the development of these cancers. The activation of autophagy and peroxisome proliferator-activated receptor gamma (PPARγ) was shown to protect colon cancer cells against apoptosis induced by the interaction between butyrate and docosahexaenoic acid (DHA) in a cell type-dependent manner. Additionally, an Atg8/LC3 family member implicated in autophagy and tumor suppression was associated with alterations to cell death and cytokine secretion in mice lacking gamma-aminobutyric acid receptor-associated protein (GABARAP). It has been well documented that inhibiting autophagy in cancer cells increases their death, with this strategy proving most useful in tumors that behave like RAS-activated tumors. Inhibiting autophagy is expected to cause ubiquitinated proteins to accumulate and p62 levels to increase; in hepatic tumors, autophagy suppresses spontaneous tumorigenesis via cell-intrinsic pathways whilst p62 accumulation promotes tumor formation.

45The elimination of damaged organelles via autophagy may allow cancer cells to survive despite the stress caused by chemotherapeutic agents. It has also been reported that upregulating autophagy after chemotherapy causes cancer cells to enter a dormant state, which may then propagate at a later stage. The state of cell cycle arrest, termed senescence, has been postulated to underlie autophagy-induced tumor cell dormancy. Ras-induced senescence is mediated by autophagy, with autophagy inhibition delaying senescence. Moreover, it has been reported that PSMD10/gankyrin stimulates autophagy in hepatocellular carcinoma (HCC) in response to starvation or stress. A physical association occurs between PSMD10 and Atg7, and is translocated to the nucleus to bind to ATG7 promote and upregulates Atg7 expression.

3.4. Autophagy in Brain Development

46There is growing evidence that autophagy performs both physiological and pathological functions in the nervous system, and that autophagic stimulation plays critical roles in neuronal survival and activity. Autophagy is the only method by which neurons degrade and excrete expired organelles, and is responsible for clearing abnormal intracytoplasmic contents from normal cells which would otherwise cause protein accumulation and damage neuronal activity, inducing severe functional impairment. Autophagy also clears protein aggregates from old neurons; thus, inhibiting autophagy can lead to neuronal degeneration and intraneuronal protein accumulation. Mutations in Atg5 confined to neural tissues can cause impaired growth, progressive motor and behavioral deficits, prominent neurodegeneration, and axonal swelling in regions of the brain with increased levels of ubiquitinylated proteins, indicating that autophagy has a neuroprotective role. In mammals, the absence of Atg59 and Atg710 can cause severe neurodegeneration, further supporting the neuroprotective role of autophagy. Furthermore, neuronal death can be attributed to the loss of basal autophagy or an imbalance in autophagic flux. In some neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and Huntington’s, as well as in the brain or spinal cord trauma, the damaged neurons exhibit abnormally high numbers of autophagosomes. Therefore, understanding the interaction between pathophysiological mechanisms and autophagy could be a promising approach for therapies against neurological disorders. Prenatal alcohol exposure has been shown to increase the number of autophagic vacuoles in the cortical micro-vessels of human fetal and mouse neonatal brains, impairing autophagy. Furthermore, autophagy can modulate Notch degradation, stem cell development, and neurogenesis.

3.5. Autophagy in Neurodegeneration

47Several reviews have evaluated the relationship between autophagy and neurodegenerative diseases. Autophagy is vital for neuronal homeostasis, and its deregulation is highly associated with numerous neurodegenerative effects, such as the accumulation of damaged and toxic molecules with pathological consequences in neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. Lysosomal system inactivation is responsible for the accumulation of autophagosomes observed in Alzheimer’s disease, whilst the disease is thought to be due to either excessive or impaired autophagosomal degradation, or the activation of autophagy genes in response to temporary injury/stress in neuronal tissues. Alzheimer’s, Parkinson’s, and Huntington’s diseases are key examples where autophagosomal accumulation and anomalies in the endosomal-lysosomal pathway have been observed in post-mortem human brain tissues via electron microscopy. Autophagy deficiency resulted in neuronal loss in the cerebral and cerebellar cortices in a mouse model. Dysfunction or abnormalities in autophagy, including mutations in autophagy-regulating genes, are accompanied by neurodegenerative diseases across the age spectrum with exceptional frequency. Atg7-deficient mice exhibited ubiquitin accumulation in their CNS, causing nervous symptoms, neurodegeneration, and ultimately death, whilst Atg5-deficient mice developed cytoplasmic inclusions and exhibited motor dysfunctions, and AMBRA 1-deficient mouse embryos displayed neuronal tube defects.

48Autophagy is involved in the cytoplasmic clearance of α-synuclein (α-syn), which is observed in Parkinson’s disease. In a mouse model, Beclin 1 overexpression was found to reduce the clearance of α-syn, leading to pathological neuron abnormalities. Pharmacological and genetic pathways are involved in the degradation of α-syn by polo-like kinase 2 via autophagy, suggesting that these two proteins are concomitantly co-degraded.

49The PINK1 and Parkin genes regulate mitophagy, indicating that mutations in these genes can cause defects in mitophagy which have been correlated with Parkinson’s disease. Beclin 1 expression is lower in the brains of patients with Alzheimer’s disease and not only affects autophagy but also increases the deposition of β-amyloid proteins causing neurodegeneration. Huntington’s disease is caused by the extension of the polyglutamine (polyQ) proteins aggregate intracellularly, which causes neuronal death. Atg-knockout C. elegans exhibit increased polyQ toxicity, whilst in Drosophila the autophagy-enhancing small molecule 2-(4-phenylphenyl)-5,6-dihydroimidazo[2,1-B][1,3] thiazole, also known as autophagy enhancer-99 (AUTEN-99), has been shown to prevent the symptoms of neurodegenerative diseases. The dual role observed for autophagy may be due to our poor understanding of this ubiquitous cellular recycling system. The differences between physiological and pathological autophagy may help design therapeutic strategies specifically targeting pathological autophagy without hindering its physiological roles. For example, the apoptosis-stimulating protein p53-2 (ASPP2/53BP2L) was reported to have different effects on autophagy in neurons stimulated with different levels of gp120, a soluble envelope glycoprotein of HIV-1 that interacts with chemokine receptors such as CXCR4 and CCR5. Thus, regulating autophagy in the CNS could be a potential therapeutic approach against HIV-associated neurocognitive disorders.

3.6.1. Autophagy in the Immune System

50The roles of cellular autophagy in immunological processes and autoimmune diseases have been reviewed extensively. Autophagy plays important roles in both innate and adaptive immunity, modulates cellular and humoral immune responses, and has roles in the non-metabolic and metabolic functions of immune cells. Furthermore, autophagy is involved in innate immune cell differentiation, degranulation, phagocytosis and extracellular trap formation involving neutrophils, eosinophils, mast cells, and natural killer cells, and plays an essential role in the renewal, differentiation, and homeostasis of immune cells. Autophagy also regulates the functional responses of immune cells, such as phagocytosis, antigen presentation, cytokine production, control of inflammasome activation, tolerance, and their consequences on overall host defense via monocytes, macrophages, dendritic cells, and antigen presentation. Additionally, autophagy plays important roles in B cell development, activation, and differentiation, which enables B cells to adapt to various events, and determines their fate, survival, and function. Since B cells produce antibodies, autophagy can determine humoral immune responses. In one study, the B cells of Atg5-deficient mice had defective antibody responses, indicating that autophagy has a role in antibody production.

Pro-Inflammatory Signaling Regulated by Autophagy

51Several studies have documented interplay between autophagy and the NF-κB signaling pathway. Members of the NF-κB family of transcription factors regulate the transcription of genes involved in cell proliferation, survival, differentiation, and development, whilst activation of the inhibitor of NF-κB (IκBα) kinase complex is essential for autophagy induction. T-cell receptor-mediated NF-κB activation in B-cell lymphoma/leukemia is linked with the autophagy adaptor p62/SQSTM1, which modulates the NLRP3-inflammasome activation and IL-1β production in macrophages.

Interplay between Cytokine Secretion and Autophagy

52IL-1α secretion is enhanced in Atg5-deficient macrophages, whilst inhibiting autophagy results in IL-1β overexpression. The anti-inflammatory cytokine, IL-10, inhibits autophagy by activating mTOR complex 1 and inhibits starvation- and IFN-γ-induced autophagy via Bcl-2 and Beclin 1 in various autoimmune and inflammatory disorders.

3.6.2. Autophagy and Autoimmunity

53Autophagy has predisposing, pathogenic, and therapeutic roles in autoimmunity. Defects in autophagy pathways and/or autophagy-related genes have been implicated in numerous autoimmune and autoinflammatory diseases, including multiple sclerosis, systemic lupus erythematosus (SLE), rheumatoid arthritis, psoriasis, psoriatic arthritis, inflammatory bowel disease, diabetes mellitus, Crohn’s disease, and vitiligo. Abnormalities in the maintenance of homeostasis via autophagy result in the accumulation of dysfunctional or defective cellular organelles, abnormal proteins, infectious agents, and metabolite accumulation. This predisposes cells to the generation of autoantibodies and proinflammatory mediators and exposes vital and susceptible cellular structures to deleterious agents that can cause disease. A recent study revealed a correlation between the expression pattern of autophagy-related genes and the type of lupus nephritis (LN); thus, autophagy could indicate of the type of LN when formulating a treatment regimen.

54Several Atgs are known to be involved in autoimmune disorders, including Atg5, PR domain zinc finger protein 1 (PRDM1; also known as BLIMP-1), and DNA-damage regulated autophagy modulator 1 (DRAM1) in SLE patients and Atg16L1 and immunity-related GTPase M (IRGM) in Crohn’s disease and ulcerative colitis. Autophagy defects have been observed in T cells, B cells, and macrophages. MHC class II antigen presentation by macrophages occurs via CMA; lysosomal proteins have a central role in antigen processing, which is essential for a correct immune system function. Studies in MRL/lpr mice which develop a full panel of lupus autoantibodies revealed that increased lysosomal pH might be an important lysosomal malfunction involved in autoimmunity, and that perturbed lysosomal turnover may lead to hyperactive antigen presentation by antigen presenting cells (APC) in autoimmune disorders.

55In innate immunity, reduced Atg5 and mTOR expression result in defective autophagy, affecting the clearance of dead cells, increasing levels of nucleic acid remnants and self-antigens, increasing type 1 IFN by DCs, and inducing B cell hyper-differentiation and autoantibody production. It has also been reported that autophagy-related gene knockdown can have therapeutic effects on autoimmune diseases. Modulating autophagy can manage immunity-related and inflammatory diseases by regulating cytokine and antibody production against immunogenic insults to prevent autoimmune diseases. Therefore, regulating autophagy has clinical potential in cancer immunotherapy, whilst autophagy and adenoviral combinations are proving beneficial in adenoviral-based oncolytic virotherapy.

3.7. Autophagy in Cardiovascular Diseases

56Under normal conditions, the myocardium exhibits low levels of autophagy, whilst stressful conditions can increase the level of autophagy to increase cell survival. Patients with congestive heart failure, coronary artery disease, hypertension, and aortic valvular disease display increased autophagosomal accumulation in their myocardial biopsies. Autophagy levels vary in normal and affected or stressed hearts, with constitutive autophagy maintaining normal structure and function, and upregulated autophagy occurring during cardiac disease or stress. In Atg5-deficient mice, contractile dysfunction and hypertrophy have been observed during cardiomyopathy, whilst cell culture studies have revealed that autophagic gene deficiency can cause the accumulation of unwanted proteins and contribute to myocardial disease. Similarly, LAMP-2-deficient mice displayed increased autophagic vacuole accumulation and could not degrade proteins, thereby promoting cardiomyopathy. It has been postulated that during early life, between birth and suckling, autophagy provides the energy required for cardiac cells, whilst mitophagy protects cardiac muscles under ischemic stress.

57Increased autophagy can cause heart failure, with autophagy-induced degeneration resulting in the death of cardiomyocytes. This knowledge has helped our understanding of the pathogenic role of autophagy in cardiac failure models and helped devise therapeutic targets. Autophagy can cause myocardial cell damage via PARP1, which promotes autophagy in cardiomyocytes by modulating FoxO3a transcription. Increased autophagy causes pathological remodeling of the heart, whilst decreased autophagy reduces remodeling. Thus, it has both protective and destructive roles in the cardiovascular system.

3.8. Autophagy in Iron Homeostasis

58Iron homeostasis involves a form of macroautophagy known as ferritinophagy, wherein ferritin, an iron storage protein, is degraded in the lysosome. Iron levels are tightly regulated in cells; nutrient deficiency induces autophagy, during which cellular proteins and organelles are engulfed by the autophagosome, which then fuses with the lysosome. The degradation of these contents provides essential resources that either promote cell survival or lead to cell death. Iron (Fe), copper (Cu), zinc (Zn), and aluminum (Al) react with molecular oxygen to produce reactive oxygen species (ROS) and reactive nitrogen species (RNS). Besides acting as a cofactor for metalloprotein enzymes involved in redox reactions, iron also plays a major role in mitochondrial ATP metabolism and other cellular processes. The Fenton and Haber-Weiss redox reaction is highly involved in ROS production and Alzheimer’s progression. To maintain iron homeostasis, storage and recycling are critical. When engulfed by macrophages, the iron within erythrocytes is either stored as a ferritin complex or exported from the cell by the ferroportin iron-exporter.

59HSP70 and ferritin bind iron in the cytosol and autophagocytosis of these proteins can sequester redox-active iron in the lysosomes. Cells rich in these proteins exhibit increased resistance to oxidative stress; therefore, autophagy plays a major role in maintaining cellular redox status. The autophagy inhibitor NCOA4, which is a substrate of PI3K, has been shown to physically bind to the ferritin protein complex and direct it to autolysosomes for degradation. NCOA4 knockdown prevents the localization of ferritin in the lysosomes and increases the levels of iron-responsive element–binding protein 2 (IRP2), which is a free intracellular Fe antagonist that prevents cell death via exogenous ROS. NCOA4 also acts as an autophagy receptor for ferritin and delivers it to the lysosome to maintain iron homeostasis. Experimentally simulating low-iron conditions by chelating iron revealed that ferritin is degraded to release the stored iron.

3.9. Autophagy in Obesity and Diabetes

60Autophagy is involved in obesity and diabetes mellitus. Improper lipid and glycogen processing can affect the liver activity and thus, insulin synthesis, resulting in diabetes. Studies have shown that hepatocytes from mouse models of obesity display reduced autophagy, with decreased Atg7 expression causing ER stress and affecting insulin signaling. Mutant Atg7 mice also exhibit reduced β cell mass, reduced insulin circulation, and glucose intolerance, indicating that autophagy defects can reduce insulin levels and cause hyperglycemia. A genetic mosaic screen for mutations that increase lysosomal and/or autophagic activity in D. melanogaster larva revealed that autophagy-lysosome pathways underlie novel cytoprotective features in Drosophila. Obesity impairs autophagy in the liver via S-nitrosylation, a process induced by nitric oxide (NO). S-nitrosylation of the lysosomal enzymes cathepsin B (CTSB) and hexosaminidase subunit β (HexB) impairs normal lysosomal functioning and is carried out by denitrosylation enzymes, particularly S-nitrosoglutathione reductase (GSNOR) and thioredoxin. Obesity inhibits the denitrosylation ability of the liver, impairing hepatic autophagy and insulin resistance. In obese animals, hepatic insulin signaling is impaired by NO-induced hepatic autophagy repression, which ultimately causes the progression of type 2 diabetes.

61The potential roles of autophagy in ameliorating diseases while maintaining homeostasis have been enumerated in Table 1. Details of applied/granted patents for treating autophagy-related ailments and dysfunctions are presented in Table 2.

3.10. Diseases Caused by Autophagy Gene Defects

62Maintaining homeostasis is the most important role of autophagy, which is the final survival mechanism used to escape cell death. Mutations or genetic dysfunctions in autophagy-associated genes can have a variety of pathological consequences, as described below:

3.10.1. Static Encephalopathy of Childhood with Neurodegeneration in Adulthood (SENDA)

63SENDA is a recently discovered type of neurodegeneration associated with iron accumulation in the brain. It begins with early-onset spastic paraplegia and mental retardation during childhood, followed by symptoms of Parkinsonism and dystonia during adulthood along with eye movement abnormalities, dysautonomia, and sleep disorders. Whole-exome next generation sequencing has revealed that SENDA is associated with a mutation in the WIPI4 gene (also known as WDR45), located at Xp11.23. The disease is characterized by iron accumulation in the globus pallidus. WIPI4, which is the mammalian homolog of yeast Atg18, is involved in autophagosome formation by binding phosphatidylinositol 3-phosphate, which is recruited to the autophagosome formation site. A severe decline in WIPI4 expression has been reported in lymphoblastoid cell lines derived from patients with SENDA. As the WIPI4 gene is found on the X chromosome, one of which undergoes inactivation in females, the loss of WIPI4 function is expressed in a mosaic pattern in females.

3.10.2. Crohn’s Disease

64Crohn’s disease is a major inflammatory bowel disease whose symptoms include abdominal pain, diarrhea, vomiting, and weight loss. Atg16L1 mutations have been found to be linked with Crohn’s disease. Atg16L1 forms a complex with Atg12-Atg5 which initiates autophagosome formation by inducing the conjugation of LC3 with PE. A study on the 300T > A Atg16L1 mutation revealed that the mutation is differentially involved in Crohn’s disease and canonical autophagy. In mice, the mutations that eliminated or reduced Atg16L1 expression indicated a relationship between Atg16L1 mutations and Crohn’s disease. Other autophagy-associated proteins, including IRGM-101, 102, and 103 and NOD2-104, 105, and 106 have also been linked to Crohn’s disease in humans. Autophagy is thought to be involved in the pathogenesis of Crohn’s disease, but it can also control disease severity by reducing the levels of inflammatory mediators.

3.10.3. Hereditary Spastic Paraparesis (HSP)

65HSP is a neurodegenerative disorder that causes axonal degeneration in the corticospinal or pyramidal motor and sensory tracts that control distal organs and is caused by a recessive mutation in the TECPR2 gene. TECPR2 interacts with six human Atg8 orthologs to positively regulate autophagy, with TECPR2 knockdown in HeLa cells reducing autophagic activity and indicating its role in autophagy. The zinc-finger protein spastizin interacts with the Beclin 1-UVRAG-Rubicon complex and is involved in autophagosome maturation. In fibroblasts derived from patients with HSP, knockout of the spastizin gene reduced autophagy and caused autophagosome accumulation by impairing lysosomal fusion. The ZFYVE26/SPASTIZIN and SPG11/SPATACSIN mutations were recently associated with HSP; however, there are currently no treatments available to reverse nerve degeneration in HSP, with efforts instead directed towards reducing symptoms by physiotherapy and improving spasticity using medication.

3.10.4. Danon Disease

66Danon disease is a rare cardiomyopathic disease caused by LAMP-2 deficiency and characterized by the accumulation of glycogen and autophagic vacuoles in cardiac and skeletal muscles, cardiomyopathy, and intellectual dysfunction. The LAMP-2 gene is alternatively spliced into three isoforms (LAMP-2A, -2B, and -2C) which have different functions in autophagy. LAMP-2A acts as a receptor for CMA, in which proteins carrying the KFERQ motif are selectively trafficked into the lysosome and degraded. LAMP-2B has been suggested to play a prominent role in macroautophagy and is responsible for the Danon phenotype. LAMP-2B-deficient mice exhibit higher mortality and autophagic vacuole accumulation in the liver, kidney, pancreas, and cardiac and skeletal muscles. Whole genome sequencing identified a nonsense mutation (codon 520C>T in exon 4) in LAMP2 in a family with Danon disease. LAMP-2 knockout resulted in failed autophagic progression, as evidenced by inappropriate cathepsin D processing in the autophagic vacuoles and abnormally high numbers of mannose-6-phosphate receptors that limited the degradation of long-lived proteins during starvation.

3.10.5. X-Linked Myopathy with Excessive Autophagy (XMEA)

67XMEA is a rare X-linked recessive skeletal myopathy caused by a single-nucleotide substitution (c. 164-7T > G) in VMA21, whose protein product assembles proton pumps in the lysosome which generate and maintain the acidity required for the activity of various lysosomal hydrolases. Impaired hydrolase activity can block the final step of autophagy or induce autophagy by inhibiting mTOR. If autophagy is impaired, a feed-forward pathogenic loop is activated, which results in the accumulation of autophagolysosomes containing incompletely-digested products. XMEA is characterized by progressive muscle weakness, particularly in the proximal muscles of the legs, and muscle degeneration (atrophy) in adulthood. Recently, two VMA21 non-coding microdeletions, one intronic (c.54-16_54-8del) and the other in the 3′UTR (c.*13_*104del), were reported to result in more severe clinical manifestations with extra-ocular and upper extremity involvement and earlier disease onset. Besides long-lived proteins and membranes, XMEA also affects membrane repair, interrupts sarcolemmal membrane homeostasis, and increases serum creatine phosphokinase (CPK) levels.

3.10.6. Sporadic Inclusion Body Myositis (sIBM)

68sIBM is an age-related progressive muscle disorder which presents in the elderly and is characterized by the presence of autophagic vacuoles and ubiquitinylated misfolded multiprotein aggregates. Two major lysosomal proteases, cathepsins D and B, exhibit decreased activation in sIBM muscle fibers whilst LC3-II is increased, indicating that autophagosome formation is increased due to reduced cathepsin D and B activity during autophagosome maturation. T cells may have a role in sIBM, whilst allelic variants of the HLA-DR3 locus, other genetic factors, and the HLA genotype are also thought to play major roles in the progression and severity of the disease. Dysphagia (difficulty in swallowing) may occur due to weakness in the neck muscles of patients with sIBM, whilst myalgia (muscle pain) and difficulty in manipulating objects may occur due to weakness in the fingers.

69An overview of diseases caused by genetic defects in autophagy genes is presented in Table 3.

4. Treatment of Autophagy-Associated Diseases

70To alleviate autophagy-associated diseases, a variety of drugs, biomolecules, chemicals, and epigenetic strategies have been developed to either promote or inhibit autophagy.

4.1. Strategies to Inhibit Autophagy

71Autophagy can be suppressed during any stage of autophagic flux. The pro-apoptotic role of autophagy may lead to hyperstimulation-induced excessive activation, which results in detrimental self-cannibalism that can go beyond the limit of cellular recovery. Numerous chemical inhibitors have been identified and tested in various cell and animal models. Most autophagy inhibitors are poorly selective, limiting their wider applications.

4.1.1. Vacuolar-Type H (+)-ATPase Inhibitors

723-methyladenine (3-MA), a class-III PI3K inhibitor, is commonly used to inhibit autophagy. Class III PI3K and Beclin 1 are essential during the first step of autophagy induction; thus, inhibiting PI3K reduces autophagosome formation. Bafilomycin A1 is a vacuolar H+-ATPase inhibitor, which functions at concentrations as low as 1 nM to inhibit both the early and late stages of autophagy by activating the mTOR pathway. In early 1998, bafilomycin A1 was reported to inhibit autophagic vacuoles in rat hepatoma by dissociating the Beclin 1-Vps34 complex and preventing autolysosome formation, thus attenuating functional autophagy. Bafilomycin A1 has been tested in a mouse model and found to be safe. Furthermore, disruption of the vacuolar-type H+-ATPase complex in mouse liver cells has been shown to induce the rapamycin complex 1 (mTORC1)-independent aggravation of autophagic vacuoles and lysosomes. Concanamycin A belongs to the same class of vacuolar H+-ATPase inhibitors as bafilomycin A1 and in the presence of autophagosomes causes autophagic bodies to accumulate in the central vacuole and cytoplasm of tobacco BY-2 cells. Therefore, vacuolar-type H+-ATPases have been proposed as potential therapeutic agents.

4.1.2. Cycloheximide

73Cycloheximide is a protein biosynthesis inhibitor that is frequently used in biomedical research. In mouse pancreatic acinar cells, cadmium chloride- or hyperosmotic sucrose-stimulated autophagy was found to be inhibited by cycloheximide, which likely inhibits autophagy at the segregation step. Cycloheximide is used to prevent the autophagy-lysosome pathway and its effects can be rapidly reversed by its removal.

4.1.3. Lysosome Alkalizers

74Chloroquine, hydroxychloroquine, NH4Cl, and neutral red are chemicals that can rapidly neutralize the acidic environment of the lysosome; therefore, they are used to block autophagosome maturation. Chloroquine and hydroxychloroquine are repurposed drugs that have been used to treat malaria, SLE, and rheumatoid arthritis; however, higher hydroxychloroquine concentrations are required to induce active autophagy as a cancer treatment, which are usually not achievable in cancer patients. Chloroquine-mediated lysosomal dysfunction is thought to have increased anti-cancer functions when combined with nutrient deprivation. Lys01, a dimeric form of chloroquine in which each molecule is separated by the spacer molecule N-bis(2-aminoethyl)-methylamine, has been reported to inhibit autophagy at a level 10-fold higher than chloroquine Lys05, a water-soluble salt of Lys01, effectively accumulates within the lysosome to concurrently deacidify and inhibit autophagy.

4.1.4. Acidic Protease Inhibitors

75Lysosomal proteases are active at an acidic pH. The protease inhibitor leupeptin inhibits cysteine, serine, and threonine peptidases to block protein degradation and thus inhibits the final step of autophagy, as evidenced by the accumulation of vacuolar autolysosomes. Cathepsins are aspartic, cysteine, and serine proteases that are transported to lysosomes via mannose-6-phosphate receptors and can be inhibited by the lysosomal protease inhibitors E64d and pepstatin A. Cathepsins B, H, and L are inhibited by E64d, whilst cathepsins D and E are inhibited by pepstatin A. Cells treated with E64d and pepstatin A exhibit increased LC3-II levels.

76Bafilomycin and chloroquine, which inhibit autophagy by targeting lysosomes, have been reported to increase levels of the autophagosome marker LC3-II, block key aspects of autophagy, decrease mitochondrial quality, and increase mitochondrial DNA damage in primary neurons.

4.1.5. Genetic Modifications

77The Atg genes are crucial in autophagy; therefore, the inactivation or knockdown of these genes may be a useful way to manipulate the process. MiR-30a has been reported to downregulate Beclin 1 and Atg5 expression, whilst miR-101 can inhibit basal and rapamycin-induced autophagy. Autophagy is induced by the activation of the ULK complex, which consists of ULK1/2, Atg13, FIP200, and Atg101. In melanoma cells, miR-290–295 clusters can inhibit ULK1 and Atg7 expression to suppress autophagic cell death. MiR-885-3p targets ULK2 to regulate autophagy, whereas miRNA-30a/b, miRNA-376b, miR-216a, miR-519a, and miR-17-5p inhibit Beclin 1 expression to suppress vesicle nucleation. Recently, the leucine-rich repeat kinase 2 gene (LRRK2), which is associated with Crohn’s disease, Parkinson’s disease, and leprosy, was shown to inhibit the non-canonical autophagy cascade, indicating that the negative regulation of this cascade could directly induce disease. In addition, the Atg16L1 300 T > A polymorphism has been demonstrated to disrupt unconventional TMEM59.110-mediated autophagy in mice.

4.2.1. Rapamycin

78Rapamycin, also known as sirolimus, is a natural mTOR inhibitor that stimulates autophagy both in vitro and in vivo; however, its long-term use is often complicated as it suppresses ribosome biogenesis and protein translation. The rapamycin ester CCI-779/Temsilorimus, which is also an mTOR inhibitor, prevents the development of intracellular tau protein inclusions (abundant protein that stabilizes microtubules in CNS neurons) which are known to accumulate in neurons in Alzheimer’s disease and other tauopathies and can also reduce the density of neurofibrillary tangles by stimulating mTOR-dependent autophagy. RAD001 and AP23573 are rapamycin derivatives with comparatively high safety and low toxicity. During the early stages of carotid atherosclerosis, which is an inflammatory step in the primary pathogenesis of cerebrovascular diseases, miRNA-155 plays an important role in the activation of autophagy by rapamycin. Rapamycin has also been shown to increase autophagy, decrease cyclin D1 expression, and attenuate aggressive IgA nephropathy progression in a rat model.

4.2.2. Small-Molecule Enhancers of Rapamycin (SMERs)

79The immunosuppressive activities of rapamycin limit its frequent use; therefore, safer molecules are required. Three SMERs were identified from 50,729 compounds that can induce autophagy; SMERs 10, 18, and 28 can reduce the pathogenesis associated with polyglutamine aggregation and A53T α-synuclein, which are linked to Huntington’s disease and familial Parkinson’s disease, respectively, and induce autophagy in an mTOR-independent manner. In addition, the small molecule AUTEN-99 activates autophagy in cell cultures and animal models and inhibits the progression of neurodegenerative symptoms.

4.2.3. Trehalose

80Trehalose is a natural disaccharide known to stimulate autophagy via AMPK. In cultured cells from an animal model of Huntington’s disease, trehalose has been shown to stimulate autophagy and reduce Huntingtin protein aggregation during starvation by inhibiting a family of glucose transporters known as the solute carrier 2 or the glucose transporter family. As well as being an autophagy activator and a non-reducing disaccharide, trehalose can also reduce the levels of aggregate-prone proteins and ameliorate cytotoxicity in neurodegenerative disease models. Trehalose treatment has been shown to increase the conversion of LC3-I to LC3-II via an mTOR-independent pathway, whilst sucrose and raffinose are also known to induce autophagy. It has been shown that trehalose can be used to safely induce autophagy in neurodegenerative disorders such as Parkinson’s disease, Alzheimer’s disease, and prion disease. The bioavailability of trehalose in the body for autophagy induction is low due to the hydrolytic enzyme, trehalase, which is expressed in the intestine and kidney; therefore, the enzyme-stable trehalose analogs, lentztrehaloses A, B, and C, were synthesized and found to be as effective as trehalose.

4.2.4. Inositol Monophosphatase (IMPase) Inhibitors

81Lithium chloride (LiCl) can induce autophagy by inhibiting inositol monophosphatase (IMPase), which reduces inositol and inositol-1,4,5-triphosphate (IP3) levels. Since lithium has already been approved by the FDA for patients with bipolar disorder, it can easily be adapted for other diseases. Long-term oral lithium administration enhanced autophagy in a tauopathy mouse model by inhibiting glycogen synthase kinase-3. L-690,330, a bisphosphonate inhibitor of IMPase, exhibits a similar function to lithium by clearing mutant synucleins and EGFP-HDQ74. Valproic acid is an angio-suppressive compound which suppresses the Akt/mTOR signaling pathway by acting as a histone deacetylase inhibitor and promotes autophagy, as evidenced by the increased concentrations of LC3-II and Beclin 1 after its administration in prostate cancer cell lines. Carbamazepine and valproic acid can both reduce intracellular inositol-1,4,5 trisphosphate levels. Therefore, other IMPase inhibitors could also be incorporated into therapeutic strategies.

4.2.5. Epigenetic Changes

82Anacardic acid, curcumin, garcinol, and spermidine increase autophagy by reducing the level of acetylation in cultured human cells, as evidenced by depleted sequestosome-1 levels and mTORC1 inhibition. Spermidine also inhibits EP300 and the major autophagy proteins, Atg5, Atg7, Atg12, and LC3 to repress autophagy. Supplementing the diet of mice with coffee beans rich in polyphenols concomitantly increased autophagy and decreased acetylation levels, whilst natural polyamines can inhibit acetyltransferases, and their dietary intake can improve the life span of short-living mouse strains and the health of long-living ones.

4.2.6. Other Molecules

83Fluoxetine, which selectively improves the secretion of the pro-inflammatory cytokine TNF-α, and gefitinib, which inhibits the epidermal growth factor receptor (EGFR), can also enhance autophagy to impart neuroprotection and restrict M. tuberculosis growth. The antiepileptic compound, carbamazepine, has been found to protect cells against M. tuberculosis infection, likely by inducing autophagy. Elevated intracytosolic Ca2+ levels can inhibit autophagy; penitrem A, which inhibits Ca2+-dependent K+ channels, is known to induce autophagy and has been used to treat neurodegenerative disorders. Furthermore, bacterial pore-forming toxins can induce the expression of the transcription factor HLH-30 (TFEB) in C. elegans, which stimulates autophagy genes and thus inhibits bacterial infection. Metformin, an AMPK activator, has been shown to induce autophagy and reduce the risk of hepatocellular carcinoma (HCC) in diabetic patients.

84A patent studied by Gorski and Qadir revealed the potential of a thioxanthone-based autophagy inhibitor for suppressing Atg gene expression by using siRNA-directed therapy against cancer cells receiving anti-cancer therapies, and for treating cancer in combination with other therapies. The use of dimeric quinacrine derivatives to inhibit lysosomes and autophagy in cancer cells where autophagy allows them to survive metabolic and therapeutic stresses is currently at the patent filing phase. The herbal product Onjisaponin B, from Radix Polygalae (Polygala tenuifolia)—a traditional Chinese herb, is known to enhance autophagy. Upon administration, it prevents, treats, or delays the onset of neurodegenerative diseases, thus a patent for this product has been granted to Law et al.. Imidazo [4–5f] phenanthroline derivatives (1–6) have been evaluated for their anti-cancer effects, with their use of upregulating LC3-II and Beclin 1 expression and thus inducing autophagy. Of the different compounds evaluated, the phenanthroimidazole 6 derivative was found to induce autophagy and apoptosis; thus, it could prove to be a novel anti-cancer drug. In nanosilica stimulated RAW264.7 cells, melatonin was found to increase LC3 expression and decrease Bax expression, suggesting that autophagy was promoted, and apoptosis was inhibited. Sasanquasaponin ΙΙΙ obtained from Schima crenata Korth was found to upregulate LC3-II expression in melanoma cells and induce autophagy; hence, it can be used as an anti-cancer drug to treat melanoma. Epigallocatechin gallate (EGCG) was found to promote autophagosome formation and increase lysosome acidification in Müller cells, thus increasing autophagy. A gliosis experimental model revealed that EGCG reduced reactive gliosis and retinal damage; hence, EGCG should be explored as a treatment of diabetic retinopathy.

85Compounds that inhibit and activate autophagy are depicted in Figure 7.

5. Concluding Remarks and Future Perspectives

86Autophagy is a fast-moving area of science which has had an excellent positive impact on animal and human health-related issues and threatening diseases and has considerable future potential. Autophagy is a highly complex process, and understanding the complexity of its mechanisms and internal regulations will be highly beneficial for developing novel methods such as simple ameba-based experimental models. Emerging studies have established many interesting connections in the field of autophagy research. Since autophagy is one of the most conserved evolutionary processes, present in lower organisms and all highly evolved mammals, much work has been carried out to understand its physiological and pathological features. Pathogenesis-associated autophagy is involved in degenerative, inflammatory, infectious, and neoplastic diseases, whereas physiological autophagy is associated with maintaining liver iron homeostasis, CNS development, endothelial cell alignment, atheroprotection, and preventing infection.

87Numerous mechanisms of action involving various signaling pathways have been linked to autophagy, with novel mechanisms currently being investigated. mTOR acts as a nutrient sensor in autophagy; however, the process may also be regulated via mTOR-independent pathways. Intracellular Ca2+ regulates autophagy, with intracellular Ca2+ mobilization via the IP3 receptor stimulating calmodulin and ERK pathways to inhibit autophagy. Notably, Ca2+ also inhibits autophagy by increasing mitochondrial ATP levels, which inhibits the CaMKKβ/AMPK pathway, yet promotes autophagy by promoting the AMPK-dependent inhibition of mTOR. Autophagy is linked with other cellular mechanisms such as apoptosis, necrosis, autosis, and necroptosis, and can take the form of microautophagy, macroautophagy, and CMA.

88Autophagy can be selective, neutralizing specific substances, or non-selective, degrading different materials irrespective of their nature. It can play physiological and pathological roles by maintaining homeostasis and causing disease, thereby affecting both health and disease. Autophagy encounters infectious and non-infectious diseases, either mediating protection or aggravating the disease. Autophagy has dual roles in an anti-bacterial, anti-viral, and tumor suppressing capacity and by favoring bacterial infections, viral infections, and tumor progression. Among its dual physio-pathological roles, autophagy can promote brain development, immunity, and cardiovascular and endocrine development, or cause neurodegeneration, autoimmune diseases, cardiovascular diseases, obesity, and diabetes.

89Autophagy has a genetic basis and many diseases are caused by genetic defects in autophagy genes, including SENDA, Crohn’s disease, HSP, Danon disease, XMEA, and sIBM.

90Efforts are being made to explore the positive aspects of autophagy to overcome various health and disease problems. Novel therapeutics and interventions are being investigated to counter autophagy-associated diseases, including apoptosis inhibitors and activators. Excessive autophagy stimulation may cause self-destruction which could be controlled with drugs such as vacuolar-type H (+)-ATPase inhibitors, cycloheximide, lysosome alkalizers (chloroquine, hydroxychloroquine, NH4Cl, and neutral red), and acidic protease inhibitors (E64d and pepstatin A), whilst knocking down Beclin 1 and Atg5 using MiR-30a could be used to inhibit the excessive cannibalism caused by autophagy. Upregulating autophagy could therapeutically benefit a range of diseases caused by reduced neuronal apoptosis, including the neurodegeneration-associated impairment of learning/memory capabilities, motor dysfunction, seizures, adult stroke, neonatal asphyxia, cardioskeletal myopathy, and cancers. Autophagy could also prevent various bacterial and viral diseases, inflammatory and autoimmune conditions, and also increase lifespan. Rapamycin, small-molecular enhancers of rapamycin (AUTEN-9), trehalose, IMPase inhibitors (carbamazepine and valproic acid), epigenetic modulators (anacardic acid, curcumin, garcinol, and spermidine), and chemicals (fluoxetine, penitrem A, and metformin) are all autophagy stimulators which help to ameliorate disorders associated with reduced autophagy.

91The apparent dual role of autophagy may be due to our poor understanding of this ubiquitous cellular recycling system. Understanding the differences between physiological and pathological autophagy may help us design therapeutic strategies to target pathological autophagy without hindering its physiological effects.

92Studies on mouse models combined with human genetic studies provide an important insight into the role of autophagy in neurological diseases like Parkinson’s and inflammatory disorders like Crohn’s disease. Some critical issues have yet to be addressed regarding the role of autophagy in therapeutics and diagnostics. There are few efficient markers for studying autophagy modulation and those that exist have limitations. These markers are important for determining the effect of autophagy on disease initiation and progression. Furthermore, autophagy modulating drugs are imprecise and nonspecific; hence, more specific drugs are required. Similarly, autophagy upregulation appears to be beneficial for removing misfolded and aggregated proteins, intracellular pathogens, damaged mitochondria, and other organelles; however, it is not yet clear how selective autophagy could be upregulated in other situations. These are just some of the questions that need to be addressed in order to use autophagy as a therapeutic molecular process. Nonetheless, autophagy modulation-based therapies will soon become a reality and will help safeguard human health against various pathological conditions.

References 519

1.
Cooper K.F. Till death do us part: The marriage of autophagy and apoptosis. Oxidative Med. Cell Longev. 2018;2018:4701275.
Not in our library10.1155/2018/4701275
2.
Mizushima N. Autophagy, process and function. Genes Dev. 2007;21:2861-2873.
Not in our library10.1101/gad.1599207
3.
Yang Z., Klionsky D.J. Mammalian autophagy, core molecular machinery and signaling regulation. Curr. Opin. Cell Biol. 2010;22:124-131.
Not in our library10.1016/j.ceb.2009.11.014
4.
Lee M.S. Overview of the minireviews on autophagy. Mol. Cells. 2018;41:1-2.
Not in our library10.14348/molcells.2018.0400
5.
Autophagy is a gatekeeper of hepatic differentiation and carcinogenesis by controlling the degradation of Yap · 2018
No notice
6.
Füllgrabe J., Ghislat C., Cho D.H., Rubinsztein D.C. Transcriptional regulation of mammalian autophagy at a glance. J. Cell Sci. 2016;129:3059-3066.
Not in our library10.1242/jcs.188920
7.
The Roles of Autophagy in Cancer · 2018
No notice
8.
Mizushima N., Levine B., Cuervo A.M., Klionsky D.J. Autophagy fights disease through cellular self-digestion. Nature. 2008;451:1069-1075.
Not in our library10.1038/nature06639
9.
Kunz J.B., Schwarz H., Mayer A. Determination of four sequential stages during microautophagy in vitro. J. Biol. Chem. 2004;279:9987-9996.
Not in our library10.1074/jbc.m307905200
10.
Li W.W., Li J., Bao J.K. Microautophagy, lesser-known self-eating. Cell. Mol. Life Sci. 2012;69:1125-1136.
Not in our library10.1007/s00018-011-0865-5
11.
Ueno T., Komatsu M. Autophagy in the liver, functions in health and disease. Nat. Rev. Gastroenterol. Hepatol. 2017;14:170-184.
Not in our library10.1038/nrgastro.2016.185
12.
Nagar R. Autophagy: A brief overview in perspective of dermatology. Indian J. Dermatol. Venereol. Leprol. 2017;83:290-297.
Not in our library10.4103/0378-6323.196320
13.
Paolini A., Omairi S., Mitchell R., Vaughan D., Matsakas A., Vaiyapuri S., Ricketts T., Rubinsztein D.C., Patel K. Attenuation of autophagy impacts on muscle fibre development, starvation induced stress and fibre regeneration following acute injury. Sci. Rep. 2018;8:9062.
Not in our library10.1038/s41598-018-27429-7
14.
Campbell P., Morris H., Schapira A. Chaperone-mediated autophagy as a therapeutic target for Parkinson disease. Expert Opin. Ther. Targets. 2018;22:823-832.
Not in our library10.1080/14728222.2018.1517156
15.
Majeski A.E., Dice J.F. Mechanisms of chaperone-mediated autophagy. Int. J. Biochem. Cell Biol. 2004;36:2435-2444.
Not in our library10.1016/j.biocel.2004.02.013
16.
Su Z., Wang T., Zhu H., Zhang P., Han R., Liu Y., Ni P., Shen H., Xu W., Xu H. HMGB1 modulates Lewis cell autophagy and promotes cell survival via RAGE-HMGB1-Erk1/2 positive feedback during nutrient depletion. Immunobiology. 2015;220:539-544.
Not in our library10.1016/j.imbio.2014.12.009
17.
Hsu P., Shi Y. Regulation of autophagy by mitochondrial phospholipids in health and diseases. Biochim. Biophys. Acta. 2017;1862:114-129.
Not in our library10.1016/j.bbalip.2016.08.003
18.
Association Between Autophagy and Neurodegenerative Diseases · 2018
No notice
19.
Huang F., Wang B.R., Wang Y.G. Role of autophagy in tumorigenesis, metastasis, targeted therapy and drug resistance of hepatocellular carcinoma. World J. Gastroenterol. 2018;24:4643-4651.
Not in our library10.3748/wjg.v24.i41.4643
20.
Pleet M.L., Branscome H., DeMarino C., Pinto D.O., Zadeh M.A., Rodriguez M., Sariyer I.K., El-Hage N., Kashanchi F. Autophagy, EVs, and infections: A perfect question for a perfect time. Front. Cell Infect. Microbiol. 2018;8:362.
Not in our library10.3389/fcimb.2018.00362
21.
Selective Autophagy and Xenophagy in Infection and Disease · 2018
No notice
22.
Hypoxia and Selective Autophagy in Cancer Development and Therapy · 2018
No notice
23.
Majdoul S., Cosette J., Seye A.K., Bernard E., Frin S., Holic N., Chazal N., Briant L., Espert L., Galy A., et al. Peptides derived from evolutionarily conserved domains in Beclin-1 and Beclin-2 enhance the entry of lentiviral vectors into human cells. J. Biol. Chem. 2017;292:18672-18681.
Not in our library10.1074/jbc.m117.800813
24.
Metaxakis A., Ploumi C., Tavernarakis N. Autophagy in age-associated neurodegeneration. Cells. 2018;7:E37.
Not in our library10.3390/cells7050037
25.
Huang C.C., Tzeng Y.M., Yeh C.T., Wu T.H.A. Method for Inhibiting Growth of Ovarian Cancer Cells. U.S. Patent. 2018.
Not in our library
26.
Apoptosis, autophagy, necroptosis, and cancer metastasis · 2015
No notice
27.
Mowers E.E., Sharifi M.N., Macleod K.F. Novel insights into how autophagy regulates tumor cell motility. Autophagy. 2016;12:1679-1680.
Not in our library10.1080/15548627.2016.1203487
28.
Janji B., Chouaib S. Role of autophagy in tumor progression and regression. Targeting Autophagy in Cancer Therapy. 2016;117-131.
Not in our library
29.
Autophagy-Regulating microRNAs and Cancer · 2017
No notice
30.
Deng Z., Purtell K., Lachance V., Wold M.S., Chen S., Yue Z. Autophagy receptors and neurodegenerative diseases. Trends Cell Biol. 2017;27:491-504.
Not in our library10.1016/j.tcb.2017.01.001
31.
Nixon R.A. The role of autophagy in neurodegenerative disease. Nat. Med. 2013;19:983-997.
Not in our library10.1038/nm.3232
32.
Becker A.C., Gannagé M., Giese S., Hu Z., Abou-Eid S., Roubaty C., Paul P., Bühler L., Gretzmeier C., Dumit V.I., et al. Influenza A virus induces autophagosomal targeting of ribosomal proteins. Mol. Cell. Proteomics. 2018;17:1909-1921.
Not in our library10.1074/mcp.ra117.000364
33.
Luo Q., Zhang L., Wei F., Fang Q., Bao F., Mi S., Li N., Wang C., Liu Y., Tu C. mTORC1 negatively regulates the replication of classical swine fever virus through autophagy and IRES-dependent translation. iScience. 2018;3:87-101.
Not in our library10.1016/j.isci.2018.04.010
34.
Khandia R., Munjal A., Dhama K., Katthik K., Tiwari R., Malik Y.P.S., Singh R.K., Chaicumpa W. Modulation of dengue/zika virus pathogenicity by antibody dependent enhancement and strategies to protect against enhancement in zika virus infection. Front. Immunol. 2018;9:597.
Not in our library10.3389/fimmu.2018.00597
35.
Peng H., Liu B., Yves T.D., He Y., Wang S., Tang H., Ren H., Zhao P., Qi Z., Qin Z. Zika virus induces autophagy in human umbilical vein endothelial cells. Viruses. 2018;10:259.
Not in our library10.3390/v10050259
36.
SARS-Coronavirus Open Reading Frame-3a drives multimodal necrotic cell death · 2018
No notice
37.
The Interplay of Viral and Host Factors in Chikungunya Virus Infection: Targets for Antiviral Strategies · 2018
Not checked
38.
Lee Y.R., Kuo S.H., Lin C.Y., Fu P.J., Lin Y.S., Yeh T.M., Liu H.S. Dengue virus-induced ER stress is required for autophagy activation, viral replication, and pathogenesis both in vitro and in vivo. Sci. Rep. 2018;8:489.
Not in our library10.1038/s41598-017-18909-3
39.
Ahmad L., Mostowy S., Sancho-Shimizu V. Autophagy-virus interplay: From cell biology to human disease. Front. Cell Dev. Biol. 2018;6:155.
Not in our library10.3389/fcell.2018.00155
40.
Barnwal B., Karlberg H., Mirazimi A., Tan Y.J. The non-structural protein of Crimean-Congo hemorrhagic fever virus disrupts the mitochondrial membrane potential and induces apoptosis. J. Biol. Chem. 2016;291:582-592.
Not in our library10.1074/jbc.m115.667436
41.
Mandhana R., Qian L.K., Horvath C.M. Constitutively active MDA5 proteins are inhibited by paramyxovirus V proteins. J. Int. Cytokine Res. 2018;38:319-332.
Not in our library10.1089/jir.2018.0049
42.
Wang Y., Jiang K., Zhang Q., Meng S., Ding C. Autophagy in negative-strand RNA virus infection. Front. Microbiol. 2018;9:206.
Not in our library10.3389/fmicb.2018.00206
43.
Martín-Acebes M.A., Blázquez A.B., Saiz J.C. Reconciling West Nile virus with the autophagic pathway. Autophagy. 2015;11:861-864.
Not in our library10.1080/15548627.2015.1037062
44.
Jones K., Patel N., Levy M., Storeygard A., Balk D., Gittleman J., Daszak P. Global trends in emerging infectious diseases. Nature. 2008;451:990-994.
Not in our library10.1038/nature06536
45.
Dhama K., Tiwari R., Chakraborty S., Kumar A., Karikalan M., Singh R., Rai R.B. Global warming and emerging infectious diseases of animals and humans: Current scenario, challenges, solutions and future perspectives—A review. Int. J. Curr. Res. 2013;5:1942-1958.
Not in our library
46.
Singh R.K., Dhama K., Malik Y.S., Ramakrishnan M.A., Karthik K., Khandia R., Tiwari R., Munjal A., Saminathan M., Sachan S., et al. Ebola virus—Epidemiology, diagnosis, and control: Threat to humans, lessons learnt, and preparedness plans—An update on its 40 year’s journey. Vet. Q. 2017;37:98-135.
Not in our library10.1080/01652176.2017.1309474
47.
Han B.A., Kramer A.M., Drake J.M. Global patterns of zoonotic disease in mammals. Trends Parasitol. 2016;32:565-577.
Not in our library10.1016/j.pt.2016.04.007
48.
Singh R.K., Dhama K., Malik Y.S., Ramakrishnan M.A., Karthik K., Tiwari R., Saurabh S., Sachan S., Joshi S.K. Zika virus—Emergence, evolution, pathology, diagnosis, and control: Current global scenario and future perspectives—A comprehensive review. Vet. Q. 2016;36:150-175.
Not in our library10.1080/01652176.2016.1188333
49.
Fabri M., Realegeno S.E., Jo E.K., Modlin R.L. Role of autophagy in the host response to microbial infection and potential for therapy. Curr. Opin. Immunol. 2011;23:65-70.
Not in our library10.1016/j.coi.2010.10.010
50.
Mitchell G., Cheng M.I., Chen C., Nguyen B.N., Whiteley A.T., Kianian S., Cox J.S., Green D.R., McDonald K.L., Portnoy D.A. Listeria monocytogenes triggers noncanonical autophagy upon phagocytosis, but avoids subsequent growth-restricting xenophagy. Proc. Natl. Acad. Sci. USA. 2018;115:E210-E217.
Not in our library10.1073/pnas.1716055115
51.
Singh V., Finke-Isami J., Hopper-Chidlaw A.C., Schwerk P., Thompson A., Tedin K. Salmonella co-opts host cell chaperone-mediated autophagy for intracellular growth. J. Biol. Chem. 2016;292:1847-1864.
Not in our library10.1074/jbc.m116.759456
52.
Roehrich A.D., Bordignon E., Mode S., Shen D.K., Liu X., Pain M., Murillo I., Martinez-Argudo I., Sessions R.B., Blocker A.J. Steps for Shigella gatekeeper protein mxic function in hierarchical type III secretion regulation. J. Biol. Chem. 2017;292:1705-1723.
Not in our library10.1074/jbc.m116.746826
53.
Bcl-xL Affects Group A Streptococcus-Induced Autophagy Directly, by Inhibiting Fusion between Autophagosomes and Lysosomes, and Indirectly, by Inhibiting Bacterial Internalization via Interaction with Beclin 1-UVRAG. · 2017
Not checked
54.
Divergent Roles of Autophagy in Virus Infection · 2013
No notice
55.
Mahima Rahal A., Deb R., Latheef S.K., Samad H.A., Tiwari R., Verma A.K., Kumar A., Dhama K. Immunomodulatory and therapeutic potentials of herbal, traditional/indigenous and ethnoveterinary medicines. Pak. J. Biol. Sci. 2012;15:754-774.
Not in our library10.3923/pjbs.2012.754.774
56.
Dhama K., Chakraborty S., Mahima Wani M.Y., Verma A.K., Deb R., Tiwari R., Kapoor S. Novel and emerging therapies safeguarding health of humans and their companion animals: A review. Pak. J. Biol. Sci. 2013;16:101-111.
Not in our library10.3923/pjbs.2013.101.111
57.
Dhama K., Chakraborty S., Wani M.Y., Tiwari R., Barathidasan R. Cytokine therapy for combating animal and human diseases—A review. Res. Opin. Anim. Vet. Sci. 2013;3:195-208.
Not in our library
58.
Dhama K., Chakraborty S., Tiwari R., Verma A.K., Saminathan M., Amarpal A., Malik Y.S., Nikousefat Z., Javdani M., Khan R.U. A concept paper on novel technologies boosting production and safeguarding health of humans and animals. Res. Opin. Anim. Vet. Sci. 2014;4:353-370.
Not in our library
59.
Dhama K., Saminathan M., Jacob S.S., Singh M., Karthik K., Amarpal A., Tiwari R., Sunkara L.T., Malik Y.S., Singh R.K. Effect of immunomodulation and immunomodulatory agents on health with some bioactive principles, modes of action and potent biomedical applications. Int. J. Pharmacol. 2015;11:253-290.
Not in our library10.3923/ijp.2015.253.290
60.
Dhama K., Latheef S.K., Munjal A.K., Khandia R., Samad H.A., Iqbal H.M.N., Joshi S.K. Probiotics in curing allergic and inflammatory conditions—Research progress and futuristic vision. Recent Pat. Inflamm. Allergy Drug Discov. 2017;10:105-118.
Not in our library10.2174/1872213x10666161226162229
61.
Malik Y.S., Sharma K., Jeena L.M., Kumar N., Sircar S., Rajak K.K., Dhama K. Toll-like receptors: The innate immune receptors with ingenious anti-viral paradigm. South Asian J. Exp. Biol. 2013;3:207-213.
Not in our library
62.
Iqbal H.M., Villalba A., Khandia R., Munjal A., Dhama K. Recent trends in nanotechnology-based drugs and formulations for targeted therapeutic delivery. Recent Pat. Inflamm. Allergy Drug Discov. 2017;10:86-93.
Not in our library10.2174/1872213x10666161213162823
63.
Khandia R., Sachan S., Munjal A.K., Tiwari R., Dhama K. Tumor Homing Peptides: Promising Futuristic Hope for Cancer Therapy. 2016;Volume 5:43-86.
Not in our library10.2174/9781681083339116050005
64.
Khandia R., Munjal A.K., Iqbal H.M., Dhama K. Heat shock proteins: Therapeutic perspectives in inflammatory disorders. Recent Pat. Inflamm. Allergy Drug Discov. 2017;10:94-104.
Not in our library10.2174/1872213x10666161213163301
65.
Mancias J.D., Kimmelman A.C. Mechanisms of selective autophagy in normal physiology and cancer. J. Mol. Biol. 2016;428:1659-1680.
Not in our library10.1016/j.jmb.2016.02.027
66.
Khambu B., Yan S., Huda N., Liu G., Yin X.M. Homeostatic role of autophagy in hepatocytes. Semin. Liver Dis. 2018;38:308-319.
Not in our library10.1055/s-0038-1669939
67.
Yang G., Driver J.P., Van Kaer L. The role of autophagy in iNKT cell development. Front. Immunol. 2018;9:2653.
Not in our library10.3389/fimmu.2018.02653
68.
Kuchitsu Y., Homma Y., Fujita N., Fukuda M. Rab7 knockout unveils regulated autolysosome maturation induced by glutamine starvation. J. Cell Sci. 2018;131:jcs215442.
Not in our library10.1242/jcs.215442
69.
Hassanpour M., Rezabakhsh A., Pezeshkian M., Rahbarghazi R., Nouri M. Distinct role of autophagy on angiogenesis: Highlights on the effect of autophagy in endothelial lineage and progenitor cells. Stem Cell Res. Ther. 2018;9:305.
Not in our library10.1186/s13287-018-1060-5
70.
From Erythroblasts to Mature Red Blood Cells: Organelle Clearance in Mammals · 2017
No notice
71.
Ahmed M., Nguyen H.Q., Hwang J.S., Zada S., Lai T.H., Kang S.S., Kim D.R. Systematic characterization of autophagy-related genes during the adipocyte differentiation using public-access data. Oncotarget. 2018;9:15526-15541.
Not in our library10.18632/oncotarget.24506
72.
Shimizu S. Biological roles of alternative autophagy. Mol. Cells. 2018;41:50-54.
Not in our library10.14348/molcells.2018.2215
73.
Mortensen M., Ferguson D.J., Edelmann M., Kessler B., Morten K.J., Komatsu M., Simon A.K. Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivo. Proc. Natl. Acad. Sci. USA. 2010;107:832-837.
Not in our library10.1073/pnas.0913170107
74.
Goldman S.J., Zhang Y., Jin S. Autophagic degradation of mitochondria in white adipose tissue differentiation. Antioxid. Redox Signal. 2011;14:1971-1978.
Not in our library10.1089/ars.2010.3777
75.
Datan E., Roy S.G., Germain G., Zali N., McLean J.E., Golshan G. Dengue-induced autophagy, virus replication and protection from cell death require ER stress (PERK) pathway activation. Cell Death Dis. 2016;7:e2127.
Not in our library10.1038/cddis.2015.409
76.
Mariño G., Niso-Santano M., Baehrecke E.H., Kroemer G. Self-consumption: The interplay of autophagy and apoptosis. Nat. Rev. Mol. Cell Biol. 2014;15:81-94.
Not in our library10.1038/nrm3735
77.
Menzies F.M., Fleming A., Caricasole A., Bento C.F., Andrews S.P., Ashkenazi A., Füllgrabe J., Jackson A., Sanchez M.J., Karabiyik C., et al. Autophagy and neurodegeneration, pathogenic mechanisms and therapeutic opportunities. Neuron. 2017;93:1015-1034.
Not in our library10.1016/j.neuron.2017.01.022
78.
Autophagy in the physiology and pathology of the central nervous system · 2014
No notice
79.
Lin L.T., Dawson P.W., Richardson C.D. Viral interactions with macroautophagy, a double-edged sword. Virology. 2010;402:1-10.
Not in our library10.1016/j.virol.2010.03.026
80.
Shoji-Kawata S., Levine B. Autophagy, antiviral immunity, and viral countermeasures. Biochim. Biophys. Acta. 2009;1793:1478-1484.
Not in our library10.1016/j.bbamcr.2009.02.008
81.
Antonioli M., Di Rienzo M., Piacentini M., Fimia G.M. Emerging mechanisms in initiating and terminating autophagy. Trends Biomed. Sci. 2017;42:28-41.
Not in our library10.1016/j.tibs.2016.09.008
82.
Yang Z., Goronzy J.J., Weyand C.M. Autophagy in autoimmune disease. J. Mol. Med. (Berl.). 2015;93:707-717.
Not in our library10.1007/s00109-015-1297-8
83.
Anding A.L., Baehrecke E.H. Cleaning house, Selective autophagy of organelles. Dev. Cell. 2017;41:10-22.
Not in our library10.1016/j.devcel.2017.02.016
84.
p62-Keap1-NRF2-ARE Pathway: A Contentious Player for Selective Targeting of Autophagy, Oxidative Stress and Mitochondrial Dysfunction in Prion Diseases · 2018
Not checked
85.
Levine B., Kroemer G. Autophagy in the pathogenesis of disease. Cell. 2008;132:27-42.
Not in our library10.1016/j.cell.2007.12.018
86.
Glick D., Barth S., Macleod K.F. Autophagy: Cellular and molecular mechanisms. J. Pathol. 2010;221:3-12.
Not in our library10.1002/path.2697
87.
Kim H.J., Lee S., Jung J.U. When autophagy meets viruses: A double-edged sword with functions in defense and offense. Semin. Immunopathol. 2010;32:323-341.
Not in our library10.1007/s00281-010-0226-8
88.
Zhu H., Tannous P., Johnstone J.L., Kong Y., Shelton J.M., Richardson J.A., Le V., Levine B., Rothermel B.A., Hill J.A. Cardiac autophagy is a maladaptive response to hemodynamic stress. J. Clin. Investig. 2007;117:1782-1793.
Not in our library10.1172/jci27523
89.
Lei Y., Zhang D., Yu J., Dong H., Zhang J., Yang S. Targeting autophagy in cancer stem cells as an anticancer therapy. Cancer Lett. 2017;393:33-39.
Not in our library10.1016/j.canlet.2017.02.012
90.
Conflict in the Intracellular Lives of Endosymbionts and Viruses: A Mechanistic Look at Wolbachia-Mediated Pathogen-blocking · 2018
No notice
91.
Levine B., Mizushima N., Virgin H.W. Autophagy in immunity and inflammation. Nature. 2011;469:323-335.
Not in our library10.1038/nature09782
92.
The Role of Mitophagy in Innate Immunity · 2018
No notice
93.
You L., Jin S., Zhu L., Qian W. Autophagy, autophagy-associated adaptive immune responses and its role in hematologic malignancies. Oncotarget. 2016;8:12374-12388.
Not in our library10.18632/oncotarget.13583
94.
Bussi C., Ramos J.M., Arroyo D.S., Gaviglio E.A., Gallea J.I., Wang J.M., Celej M.S., Iribarren P. Autophagy down regulates pro-inflammatory mediators in BV2 microglial cells and rescues both LPS and alpha-synuclein induced neuronal cell death. Sci. Rep. 2017;7:43153.
Not in our library10.1038/srep43153
95.
Ye J., Jiang Z., Chen X., Liu M., Li J., Liu N. The role of autophagy in pro-inflammatory responses of microglia activation via mitochondrial reactive oxygen species in vitro. J. Neurochem. 2017;142:215-230.
Not in our library10.1111/jnc.14042
96.
Kissová I., Salin B., Schaeffer J., Bhatia S., Manon S., Camougrand N. Selective and non-selective autophagic degradation of mitochondria in yeast. Autophagy. 2007;3:329-336.
Not in our library10.4161/auto.4034
97.
Zaffagnini G., Martens S. Mechanisms of selective autophagy. J. Mol. Biol. 2016;428:1714-1724.
Not in our library10.1016/j.jmb.2016.02.004
98.
Pierzynowska K., Gaffke L., Cyske Z., Puchalski M., Rintz E., Bartkowski M., Osiadły M., Pierzynowski M., Mantej J., Piotrowska E., et al. Autophagy stimulation as a promising approach in treatment of neurodegenerative diseases. Metab. Brain Dis. 2018;33:989-1008.
Not in our library10.1007/s11011-018-0214-6
99.
Moulis M., Vindis C. Autophagy in metabolic age-related human diseases. Cells. 2018;7:149.
Not in our library10.3390/cells7100149
100.
Liao G., Yao Y., Liu J., Yu Z., Cheung S., Xie A., Liang X., Bi X. Cholesterol accumulation is associated with lysosomal dysfunction and autophagic stress in Npc1−/− mouse brain. Am. J. Pathol. 2007;171:962-975.
Not in our library10.2353/ajpath.2007.070052
101.
Chang T.Y., Reid P.C., Sugii S., Ohgami N., Cruz J.C., Chang C.C. Niemann-Pick type C disease and intracellular cholesterol trafficking. J. Biol. Chem. 2005;280:20917-20920.
Not in our library10.1074/jbc.r400040200
102.
Vance J.E. Lipid imbalance in the neurological disorder, Niemann-Pick C disease. FEBS Lett. 2006;580:5518-5524.
Not in our library10.1016/j.febslet.2006.06.008
103.
Battu S., Afroz S., Giddaluru J., Naz S., Huang W., Khumukcham S.S., Khan R.A., Bhat S.Y., Qureshi I.A., Manavathi B., et al. Amino acid starvation sensing dampens IL-1β production by activating riboclustering and autophagy. PLoS Biol. 2018;16:e2005317.
Not in our library10.1371/journal.pbio.2005317
104.
Congdon E.E. Sex differences in autophagy contribute to female vulnerability in Alzheimer’s disease. Front. Neurosci. 2018;12:372.
Not in our library10.3389/fnins.2018.00372
105.
Joy S., Thirunavukkarasu L., Agrawal P., Singh A., Sagar B., Manjithaya R., Surolia N. Basal and starvation-induced autophagy mediates parasite survival during intraerythrocytic stages of Plasmodium falciparum. Cell Death Discov. 2018;4:43.
Not in our library10.1038/s41420-018-0107-9
106.
Intracellular Cholesterol Trafficking and Impact in Neurodegeneration · 2017
No notice
107.
Zhu J.H., Horbinski C., Guo F., Watkins S., Uchiyama Y., Chu C.T. Regulation of autophagy by extracellular signal-regulated protein kinases during 1-methyl-4-phenylpyridinium-induced cell death. Am. J. Pathol. 2007;170:75-86.
Not in our library10.2353/ajpath.2007.060524
108.
Crosstalk between Autophagy and Apoptosis: Potential and Emerging Therapeutic Targets for Cardiac Diseases · 2016
No notice
109.
Li S.J., Sun S.J., Gao J., Sun F.B. Wogonin induces Beclin-1/PI3K and reactive oxygen species-mediated autophagy in human pancreatic cancer cells. Oncol. Lett. 2016;12:5059-5067.
Not in our library10.3892/ol.2016.5367
110.
Hurley J.H., Young L.N. Mechanisms of autophagy initiation. Ann. Rev. Biochem. 2017;86:225-244.
Not in our library10.1146/annurev-biochem-061516-044820
111.
Frankel L.B., Lubas M., Lund A.H. Emerging connections between RNA and autophagy. Autophagy. 2016;13:3-23.
Not in our library10.1080/15548627.2016.1222992
112.
Song S., Tan J., Miao Y., Li M., Zhang Q. Crosstalk of autophagy and apoptosis: Involvement of the dual role of autophagy under ER stress. J. Cell Physiol. 2017;232:2977-2984.
Not in our library10.1002/jcp.25785
113.
Fujiwara Y., Wada K., Kabuta T. Lysosomal degradation of intracellular nucleic acids-multiple autophagic pathways. J. Biochem. 2017;161:145-154.
Not in our library10.1093/jb/mvw085
114.
Yin Z., Klionsky D.J. HS1BP3 provides a novel mechanism of negative autophagy regulation through membrane lipids. Autophagy. 2017;13:779-780.
Not in our library10.1080/15548627.2017.1305534
115.
Kumsta C., Hansen M. Hormetic heat shock and HSF-1 overexpression improve C. elegans survival and proteostasis by inducing autophagy. Autophagy. 2017;13:1076-1077.
Not in our library10.1080/15548627.2017.1299313
116.
Shin H.J., Kim H., Kim K.I., Baek S.H. Epigenetic and transcriptional regulation of autophagy. Autophagy. 2016;12:2248-2249.
Not in our library10.1080/15548627.2016.1214780
117.
Tavera-Mendoza L.E., Westerling T., Libby E., Marusyk A., Cato L., Cassani R., Cameron L.A., Ficarro S.B., Marto J.A., Klawitter J., et al. Vitamin D receptor regulates autophagy in the normal mammary gland and in luminal breast cancer cells. Proc. Natl. Acad. Sci. USA. 2017;114:E2186-E2194.
Not in our library10.1073/pnas.1615015114
118.
Huber L.A., Teis D. Lysosomal signaling in control of degradation pathways. Curr. Opin. Cell Biol. 2016;39:8-14.
Not in our library10.1016/j.ceb.2016.01.006
119.
Monitoring and Measuring Autophagy · 2017
No notice
120.
Fukuda T., Kanki T. Mechanisms and physiological roles of mitophagy in yeast. Mol. Cells. 2018;41:35-44.
Not in our library10.14348/molcells.2018.2214
121.
Isakson P., Holland P., Simonsen A. The role of Alfy in selective autophagy. Cell Death Differ. 2013;20:12-20.
Not in our library10.1038/cdd.2012.66
122.
Tallóczy Z., Jiang W., Virgin H.W., Leib D.A., Scheuner D., Kaufman R.J., Eskelinen E.L., Levine B. Regulation of starvation-and virus-induced autophagy by the eif2α kinase signaling pathway. Proc. Natl. Acad. Sci. USA. 2002;99:190-195.
Not in our library10.1073/pnas.012485299
123.
Youle R.J., Narendra D.P. Mechanisms of mitophagy. Nat. Rev. Mol. Cell Biol. 2011;12:9-14.
Not in our library10.1038/nrm3028
124.
Okamoto K., Kondo-Okamoto N., Ohsumi Y. Mitochondria-anchored receptor Atg32 mediates degradation of mitochondria via selective autophagy. Dev. Cell. 2009;17:87-97.
Not in our library10.1016/j.devcel.2009.06.013
125.
Ding W.X., Yin X.M. Mitophagy: Mechanisms, pathophysiological roles, and analysis. Biol. Chem. 2012;393:547-564.
Not in our library10.1515/hsz-2012-0119
126.
Kanki T., Wang K., Cao Y., Baba M., Klionsky D.J. Atg32 is a mitochondrial protein that confers selectivity during mitophagy. Dev. Cell. 2009;17:98-109.
Not in our library10.1016/j.devcel.2009.06.014
127.
Novak I., Kirkin V., McEwan D.G., Zhang J., Wild P., Rozenknop A. Nix is a selective autophagy receptor for mitochondrial clearance. EMBO Rep. 2010;11:45-51.
Not in our library10.1038/embor.2009.256
128.
Novak I., Dikic I. Autophagy receptors in developmental clearance of mitochondria. Autophagy. 2011;7:301-303.
Not in our library10.4161/auto.7.3.14509
129.
Hutchins M.U., Veenhuis M., Klionsky D.J. Peroxisome degradation in Saccharomyces cerevisiae is dependent on machinery of macroautophagy and the Cvt pathway. J. Cell Sci. 1999;112:4079-4087.
Not in our library10.1242/jcs.112.22.4079
130.
Nazarko T.Y., Farré J.C., Subramani S. Peroxisome size provides insights into the function of autophagy-related proteins. Mol. Biol. Cell. 2009;20:3828-3939.
Not in our library10.1091/mbc.e09-03-0221
131.
Yamasaki A., Noda N.N. Structural biology of the Cvt pathway. J. Mol. Biol. 2017;429:531-542.
Not in our library10.1016/j.jmb.2017.01.003
132.
Molino D., Zemirli N., Codogno P., Morel E. The journey of the autophagosome through mammalian cell organelles and membranes. J. Mol. Biol. 2016;429:497-514.
Not in our library10.1016/j.jmb.2016.12.013
133.
Sahu R., Kaushik S., Clement C.C., Cannizzo E.S., Scharf B., Follenzi A., Potolicchio I., Nieves E., Cuervo A.M., Santambrogio L. Microautophagy of cytosolic proteins by late endosomes. Dev. Cell. 2011;20:131-139.
Not in our library10.1016/j.devcel.2010.12.003
134.
Yarana C., St Clair D.K. Chemotherapy-induced tissue injury, an insight into the role of extracellular vesicles-mediated oxidative stress responses. Antioxidants. 2017;6:75.
Not in our library10.3390/antiox6040075
135.
Dice J.F. Peptide sequences that target cytosolic proteins for lysosomal proteolysis. Trends Biochem. Sci. 1990;15:305-309.
Not in our library10.1016/0968-0004(90)90019-8
136.
Tasset I., Cuervo A.M. Role of chaperone-mediated autophagy in metabolism. FEBS J. 2016;283:2403-2413.
Not in our library10.1111/febs.13677
137.
Cuervo A.M., Dice J.F. A receptor for the selective uptake and degradation of proteins by lysosomes. Science. 1996;273:501-503.
Not in our library10.1126/science.273.5274.501
138.
Lee J., Ye Y. The roles of endo-lysosomes in unconventional protein secretion. Cells. 2018;7:E198.
Not in our library10.3390/cells7110198
139.
Bandyopadhyay U., Kaushik S., Varticovski L., Cuervo A.M. The chaperone-mediated autophagy receptor organizes in dynamic protein complexes at the lysosomal membrane. Mol. Cell. Biol. 2008;28:5747-5763.
Not in our library10.1128/mcb.02070-07
140.
Kaushik S., Cuervo A.M. Methods to monitor chaperone-mediated autophagy. Methods Enzymol. 2009;452:297-324.
Not in our library10.1016/s0076-6879(08)03619-7
141.
Orvedahl A., Macpherson S., Sumpter R., Tallóczy Z., Zou Z., Levine B. Autophagy protects against sindbis virus infection of the central nervous system. Cell Host Microbe. 2010;7:115-127.
Not in our library10.1016/j.chom.2010.01.007
142.
Egger D., Wölk B., Gosert R., Bianchi L., Blum H.E., Moradpour D., Bienz K. Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex. J. Virol. 2002;76:5974-5984.
Not in our library10.1128/jvi.76.12.5974-5984.2002
143.
Lee Y.R., Lei H.Y., Liu M.T., Wang J.R., Chen S.H., Jiang-Shieh Y.F., Lin Y.S., Yeh T.M., Liu C.C., Liu H.S. Autophagic machinery activated by dengue virus enhances virus replication. Virology. 2008;374:240-248.
Not in our library10.1016/j.virol.2008.02.016
144.
Subversion of Cellular Autophagosomal Machinery by RNA Viruses · 2005
No notice
145.
Balvers R., Jiang H., Piya S., Gomez-Manzano C., Fueyo J. Adenovirus, autophagy and lysis: Ecstasies and agonies. Future Virol. 2011;6:1161-1164.
Not in our library10.2217/fvl.11.93
146.
Yang Z., Zhong L., Zhong S., Xian R., Yuan B. Hypoxia induces microglia autophagy and neural inflammation injury in focal cerebral ischemia model. Exp. Mol. Pathol. 2015;98:219-224.
Not in our library10.1016/j.yexmp.2015.02.003
147.
Tang Y., Jacobi A., Vater C., Zou L., Zou X., Stiehler M. Icariin promotes angiogenic differentiation and prevents oxidative stress-induced autophagy in endothelial progenitor cells. Stem Cells. 2015;33:1863-1877.
Not in our library10.1002/stem.2005
148.
Fu Q., Shi H., Ren Y., Guo F., Ni W., Qiao J., Wang P., Zhang H., Chen C. Bovine viral diarrhea virus infection induces autophagy in MDBK cells. J. Microbiol. 2014;52:619-625.
Not in our library10.1007/s12275-014-3479-4
149.
Lee W.S., Sung M.S., Lee E.G., Yoo H.G., Cheon Y.H., Chae H.J., Yoo W.H. A pathogenic role for ER stress-induced autophagy and ER chaperone GRP78/BiP in T lymphocyte systemic lupus erythematosus. J. Leukoc. Biol. 2015;97:425-433.
Not in our library10.1189/jlb.6a0214-097r
150.
Kamada Y., Yoshino K., Kondo C., Kawamata T., Oshiro N., Yonezawa K., Ohsumi Y. Tor directly controls the Atg1 kinase complex to regulate autophagy. Mol Cell Biol. 2010;30:1049-1058.
Not in our library10.1128/mcb.01344-09
151.
Hara T., Mizushima N. Role of ULK-FIP200 complex in mammalian autophagy: FIP200, a counterpart of yeast Atg17? Autophagy. 2009;5:85-87.
Not in our library10.4161/auto.5.1.7180
152.
Mizushima N. The role of the Atg1/ULK1 complex in autophagy regulation. Curr. Opin. Cell Biol. 2010;22:132-139.
Not in our library10.1016/j.ceb.2009.12.004
153.
Lin M.G., Hurley J.H. Structure and function of the ULK1 complex in autophagy. Curr. Opin. Cell Biol. 2016;39:61-68.
Not in our library10.1016/j.ceb.2016.02.010
154.
Mizushima N., Komatsu M. Autophagy, renovation of cells and tissues. Cell. 2011;147:728-741.
Not in our library10.1016/j.cell.2011.10.026
155.
A molecular perspective of mammalian autophagosome biogenesis · 2018
No notice
156.
Yu L., McPhee C.K., Zheng L., Mardones G.A., Rong Y., Peng J., Mi N., Zhao Y., Liu Z., Wan F., et al. Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature. 2010;465:942-946.
Not in our library10.1038/nature09076
157.
Kaur J., Debnath J. Autophagy at the crossroads of catabolism and anabolism. Nat. Rev. Mol. Cell Biol. 2015;16:461-472.
Not in our library10.1038/nrm4024
158.
Herb M., Gluschko A., Schramm M. LC3-associated phagocytosis—The highway to hell for phagocytosed microbes. Semin. Cell Dev. Biol. 2019.
Not in our library10.1016/j.semcdb.2019.04.016
159.
Bader C.A., Shandala T., Ng Y.S., Johnson I.R., Brooks D.A. Atg9 is required for intraluminal vesicles in amphisomes and autolysosomes. Biol. Open. 2015;4:1345-1355.
Not in our library10.1242/bio.013979
160.
Mari M., Griffith J., Rieter E., Krishnappa L., Klionsky D.J., Reggiori F. An Atg9-containing compartment that functions in the early steps of autophagosome biogenesis. J. Cell Biol. 2010;190:1005-1022.
Not in our library10.1083/jcb.200912089
161.
Maron B.J., Roberts W.C., Arad M., Haas T.S., Spirito P., Wright G.B., Almquist A.K., Baffa J.M., Saul J.P., Ho C.Y., et al. Clinical outcome and phenotypic expression in LAMP2 cardiomyopathy. JAMA. 2009;301:1253-1259.
Not in our library10.1001/jama.2009.371
162.
Holland P., Knævelsrud H., Søreng K., Mathai B.J., Lystad A.H., Pankiv S., Bjørndal G.T., Schultz S.W., Lobert V.H., Chan R.B., et al. HS1BP3 negatively regulates autophagy by modulation of phosphatidic acid levels. Nat. Commun. 2016;7:13889.
Not in our library10.1038/ncomms13889
163.
Wen H., Zhan L., Chen S., Long L., Xu E. Rab7 may be a novel therapeutic target for neurologic diseases as a key regulator in autophagy. J. Neurosci. Res. 2017;95:1993-2004.
Not in our library10.1002/jnr.24034
164.
Zhang L., Dai F., Cui L., Zhou B., Guo Y. Up-regulation of the active form of small GTPase Rab13 promotes macroautophagy in vascular endothelial cells. Biochim. Biophys. Acta Mol. Cell Res. 2017;1864:613-624.
Not in our library10.1016/j.bbamcr.2017.01.003
165.
Behrends C., Sowa M.E., Gygi S.P., Harper J.W. Network organization of the human autophagy system. Nature. 2010;466:68-76.
Not in our library10.1038/nature09204
166.
McKnight N.C., Jefferies H.B.J., Alemu E.A., Saunders R.E., Howell M., Johansen T., Tooze S.A. Genome-wide siRNA screen reveals amino acid starvation-induced autophagy requires SCOC and WAC. EMBO J. 2012;31:1931-1946.
Not in our library10.1038/emboj.2012.36
167.
Guo B., Huang X., Zhang P., Qi L., Liang Q., Zhang X., Huang J., Fang B., Hou W., Han J., et al. Genome-wide screen identifies signalling pathways that regulate autophagy during Caenorhabditis elegans development. EMBO Rep. 2014;15:705-713.
Not in our library10.1002/embr.201338310
168.
Autosis and autophagic cell death: the dark side of autophagy · 2014
No notice
169.
Liu Y., Shoji-Kawata S., Sumpter R.M., Wei Y., Ginet V., Zhang L., Posner B., Tran K.A., Green D.R., Xavier R.J., et al. Autosis is a Na+, K+-ATPase-regulated form of cell death triggered by autophagy-inducing peptides, starvation, and hypoxia-ischemia. Proc. Natl. Acad. Sci. USA. 2013;110:20364-20371.
Not in our library10.1073/pnas.1319661110
170.
Shoji-Kawata S., Sumpter R., Leveno M., Campbell G.R., Zou Z., Kinch L., Wilkins A.D., Sun Q., Pallauf K., MacDuff D., et al. Identification of a candidate therapeutic autophagy-inducing peptide. Nature. 2013;494:201-206.
Not in our library10.1038/nature11866
171.
Muñoz-Pinedo C., Martin S.J. Autosis, a new addition to the cell death Tower of Babel. Cell Death Dis. 2014;5:e1319.
Not in our library10.1038/cddis.2014.246
172.
Puyal J., Ginet V., Clarke P.G. Multiple interacting cell death mechanisms in the mediation of excitotoxicity and ischemic brain damage, a challenge for neuroprotection. Prog. Neurobiol. 2013;105:24-48.
Not in our library10.1016/j.pneurobio.2013.03.002
173.
Kheloufi M., Boulanger C.M., Codogno P., Rautou P.E. Autosis occurs in the liver of patients with severe anorexia nervosa. Hepatology. 2015;62:657-658.
Not in our library10.1002/hep.27597
174.
Matsui Y., Takagi H., Qu X., Abdellatif M., Sakoda H., Asano T., Levine B., Sadoshima J. Distinct roles of autophagy in the heart during ischemia and reperfusion: Roles of AMP-activated protein kinase and Beclin 1 in mediating autophagy. Circ. Res. 2007;100:914-922.
Not in our library10.1161/01.res.0000261924.76669.36
175.
Fitzwalter B.E., Thorburn A. Recent insights into cell death and autophagy. FEBS J. 2015;282:4279-4288.
Not in our library10.1111/febs.13515
176.
Liang X.H., Kleeman L.K., Jiang H.H., Gordon G., Goldman J.E., Berry G., Herman B., Levine B. Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein. J. Virol. 1998;72:8586-8596.
Not in our library10.1128/jvi.72.11.8586-8596.1998
177.
The Bcl-2 Family in Host-Virus Interactions · 2017
Not checked
178.
Beclin 1 Phosphorylation – at the Center of Autophagy Regulation · 2018
No notice
179.
Pattingre S., Tassa A., Qu X., Garuti R., Liang X.H., Mizushima N., Packer M., Schneider M.D., Levine B. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell. 2005;122:927-939.
Not in our library10.1016/j.cell.2005.07.002
180.
p53-Mediated Molecular Control of Autophagy in Tumor Cells · 2018
No notice
181.
Mizushima N., Yoshimorim T., Levine B. Methods in mammalian autophagy research. Cell. 2010;140:313-326.
Not in our library10.1016/j.cell.2010.01.028
182.
Rubinstein A.D., Eisenstein M., Ber Y., Bialik S., Kimchi A. The autophagy protein Atg12 associates with antiapoptotic Bcl-2 family members to promote mitochondrial apoptosis. Mol. Cell. 2011;44:698-709.
Not in our library10.1016/j.molcel.2011.10.014
183.
Gump J.M., Thorburn A. Sorting cells for basal and induced autophagic flux by quantitative ratiometric flow cytometry. Autophagy. 2014;10:1327-1334.
Not in our library10.4161/auto.29394
184.
Thorburn J., Andrysik Z., Staskiewicz L., Gump J., Maycotte P., Oberst A., Green D.R., Espinosa J.M., Thorburn A. Autophagy controls the kinetics and extent of mitochondrial apoptosis by regulating PUMA levels. Cell Rep. 2014;7:45-52.
Not in our library10.1016/j.celrep.2014.02.036
185.
Nezis I.P., Shravage B.V., Sagona A.P., Johansen T., Baehrecke E.H., Stenmark H. Autophagy as a trigger for cell death: Autophagic degradation of inhibitor of apoptosis dBruce controls DNA fragmentation during late oogenesis in Drosophila. Autophagy. 2010;6:1214-1215.
Not in our library10.4161/auto.6.8.13694
186.
Oami T., Watanabe E., Hatano M., Sunahara S., Fujimura L., Sakamoto A., Ito C., Toshimori K., Oda S. Suppression of T cell autophagy results in decreased viability and function of T cells through accelerated apoptosis in a murine sepsis model. Crit. Care Med. 2017;45:e77-e85.
Not in our library10.1097/ccm.0000000000002016
187.
Xu X., Xu J., Shi S., Wang Q., Saxton B., Xing C., Lin Y. Combination of TRAIL and Chal-24 synergistically induces autophagy-mediated apoptosis in lung cancer cells. Clin. Cancer Res. 2017;23(Suppl. 1):A06.
Not in our library
188.
Bonapace L., Bornhauser B.C., Schmitz M., Cario G., Ziegler U., Niggli F.K., Schäfer B.W., Schrappe M., Stanulla M., Bourquin J.P. Induction of autophagy-dependent necroptosis is required for childhood acute lymphoblastic leukemia cells to overcome glucocorticoid resistance. J. Clin. Investig. 2010;120:1310-1323.
Not in our library10.1172/jci39987
189.
Bell B.D., Leverrier S., Weist B.M., Newton R.H., Arechiga A.F., Luhrs K.A., Morrissette N.S., Walsh C.M. FADD and caspase-8 control the outcome of autophagic signaling in proliferating T cells. Proc. Natl. Acad. Sci. USA. 2008;105:16677-16682.
Not in our library10.1073/pnas.0808597105
190.
Farkas T., Daugaard M., Jäättelä M. Identification of small molecule inhibitors of phosphatidylinositol 3-kinase and autophagy. J. Biol. Chem. 2011;286:38904-38912.
Not in our library10.1074/jbc.m111.269134
191.
Osborn S.L., Diehl G., Han S.J., Xue L., Kurd N., Hsieh K., Cado D., Robey E.A., Winoto A. Fas-associated death domain (FADD) is a negative regulator of T-cell receptor-mediated necroptosis. Proc. Natl. Acad. Sci. USA. 2010;107:13034-13039.
Not in our library10.1073/pnas.1005997107
192.
Ni H.M., McGill M.R., Chao X., Woolbright B.L., Jaeschke H., Ding W.X. Caspase inhibition prevents tumor necrosis factor-α-induced apoptosis and promotes necrotic cell death in mouse hepatocytes in vivo and in vitro. Am. J. Pathol. 2016;186:2623-2636.
Not in our library10.1016/j.ajpath.2016.06.009
193.
Sun L., Li B., Su X., Chen G., Li Y., Yu L., Li L., Wei W. An ursolic acid derived small molecule triggers cancer cell death through hyperstimulation of macropinocytosis. J. Med. Chem. 2017;60:6638-6648.
Not in our library10.1021/acs.jmedchem.7b00592
194.
Wu Y.T., Tan H.L., Huang Q., Sun X.J., Zhu X., Shen H.M. zVAD-induced necroptosis in L929 cells depends on autocrine production of TNFα mediated by the PKC-MAPKs-AP-1 pathway. Cell Death Differ. 2011;18:26-37.
Not in our library10.1038/cdd.2010.72
195.
Milne J.C., Denu J.M. The sirtuin family, therapeutic targets to treat diseases of aging. Curr. Opin. Chem. Biol. 2008;12:11-17.
Not in our library10.1016/j.cbpa.2008.01.019
196.
Zhao Y., Wang L., Yang J., Zhang P., Ma K., Zhou J., Liao W., Zhu W.G. Antineoplastic activity of the cytosolic FoxO1 results from autophagic cell death. Autophagy. 2010;6:988-990.
Not in our library10.4161/auto.6.7.13289
197.
Moriwaki K., Chan F.K. RIP3, a molecular switch for necrosis and inflammation. Genes Dev. 2013;27:1640-1649.
Not in our library10.1101/gad.223321.113
198.
Liao Z., Dai Z., Cai C., Zhang X., Li A., Zhang H., Yan Y., Lin W., Wu Y., Li H., et al. Knockout of Atg5 inhibits proliferation and promotes apoptosis of DF-1 cells. In Vitro Cell Dev. Biol. Anim. 2019;55:341-348.
Not in our library10.1007/s11626-019-00342-7
199.
Goodall M.L., Fitzwalter B.E., Zahedi S., Wu M., Rodriguez D., Mulcahy-Levy J.M., Green D.R., Morgan M., Cramer S.D., Thorburn A. The autophagy machinery controls cell death switching between apoptosis and necroptosis. Dev. Cell. 2016;37:337-349.
Not in our library10.1016/j.devcel.2016.04.018
200.
Kharaziha P., Chioureas D., Baltatzis G., Fonseca P., Rodriguez P., Gogvadze V., Lennartsson L., Björklund A.C., Zhivotovsky B., Grandér D., et al. Sorafenib-induced defective autophagy promotes cell death by necroptosis. Oncotarget. 2015;6:37066-37082.
Not in our library10.18632/oncotarget.5797
201.
Pajuelo D., Gonzalez-Juarbe N., Tak U., Sun J., Orihuela C.J., Niederweis M. NAD+ depletion triggers macrophage necroptosis, a cell death pathway exploited by Mycobacterium tuberculosis. Cell Rep. 2018;24:429-440.
Not in our library10.1016/j.celrep.2018.06.042
202.
Caruso L.B., Martin K.A., Lauretti E., Hulse M., Siciliano M., Lupey-Green L.N., Abraham A., Skorski T., Tempera I. Poly(ADP-ribose) polymerase 1, PARP1, modifies EZH2 and inhibits EZH2 histone methyltransferase activity after DNA damage. Oncotarget. 2018;9:10585-10605.
Not in our library10.18632/oncotarget.24291
203.
He S., Wang L., Miao L., Wang T., Du F., Zhao L., Wang X. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell. 2009;137:1100-1111.
Not in our library10.1016/j.cell.2009.05.021
204.
Srivastava R.A.K., Pinkosky S.L., Filippov S., Abdellatif M., Sakoda H., Asano T., Levine B., Sadoshima J. AMP-activated protein kinase, an emerging drug target to regulate imbalances in lipid and carbohydrate metabolism to treat cardio-metabolic diseases. J. Lipid Res. 2012;53:2490-2514.
Not in our library10.1194/jlr.r025882
205.
Alers S., Löffler A.S., Wesselborg S., Stork B. Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: Cross talk, shortcuts, and feedbacks. Mol. Cell. Biol. 2012;32:2-11.
Not in our library10.1128/mcb.06159-11
206.
Alexander A., Cai S.L., Kim J., Nanez A., Sahin M., MacLean K.H., Inoki K., Guan K.L., Shen J., Person M.D., et al. ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS. Proc. Natl. Acad. Sci. USA. 2010;107:4153-4158.
Not in our library10.1073/pnas.0913860107
207.
Birmingham C.L., Brumell J.H. Autophagy recognizes intracellular Salmonella enterica serovar Typhimurium in damaged vacuoles. Autophagy. 2006;2:156-158.
Not in our library10.4161/auto.2825
208.
Yoshikawa Y., Ogawa M., Hain T., Chakraborty T., Sasakawa C. Listeria monocytogenes ActA is a key player in evading autophagic recognition. Autophagy. 2009;5:1220-1221.
Not in our library10.4161/auto.5.8.10177
209.
Krokowski S., Mostowy S. Interactions between Shigella flexneri and the autophagy machinery. Front. Cell Infect. Microbiol. 2016;6:17.
Not in our library10.3389/fcimb.2016.00017
210.
Nakagawa I., Amano A., Mizushima N., Yamamoto A., Yamaguchi H., Kamimoto T., Nara A., Funao J., Nakata M., Tsuda K., et al. Autophagy defends cells against invading group A Streptococcus. Science. 2004;306:1037-1040.
Not in our library10.1126/science.1103966
211.
Philpott D.J., Sorbara M.T., Robertson S.J., Croitoru K., Girardin S.E. NOD proteins: Regulators of inflammation in health and disease. Nat. Rev. Immunol. 2014;14:9-23.
Not in our library10.1038/nri3565
212.
Sorbara M.T., Ellison L.K., Ramjeet M., Travassos L.H., Jones N.L., Girardin S.E., Philpott D.J. The protein ATG16L1 suppresses inflammatory cytokines induced by the intracellular sensors Nod1 and Nod2 in an autophagy-independent manner. Immunity. 2013;39:858-873.
Not in our library10.1016/j.immuni.2013.10.013
213.
Deretic V., Saitoh T., Akira S. Autophagy in infection, inflammation and immunity. Nat. Rev. Immunol. 2013;13:722-737.
Not in our library10.1038/nri3532
214.
Jia K., Thomas C., Akbar M., Sun Q., Adams-Huet B., Gilpin C., Levine B. Autophagy genes protect against Salmonella typhimurium infection and mediate insulin signaling-regulated pathogen resistance. Proc. Natl. Acad. Sci. USA. 2009;106:14564-14569.
Not in our library10.1073/pnas.0813319106
215.
Chen H.D., Kao C.Y., Liu B.Y., Huang S.W., Kuo C.J., Ruan J.W., Lin Y.H., Huang C.R., Chen Y.H., Wang H.D., et al. HLH-30/TFEB-mediated autophagy functions in a cell-autonomous manner for epithelium intrinsic cellular defense against bacterial pore-forming toxin in C. elegans. Autophagy. 2017;13:371-385.
Not in our library10.1080/15548627.2016.1256933
216.
Kim J.K., Lee H.M., Park K.S., Shin D.M., Kim T.S., Kim Y.S., Suh H.W., Kim S.Y., Kim I.S., Kim J.M., et al. MIR144* inhibits antimicrobial responses against Mycobacterium tuberculosis in human monocytes and macrophages by targeting the autophagy protein DRAM2. Autophagy. 2017;13:423-441.
Not in our library10.1080/15548627.2016.1241922
217.
Wu Y., Wang Y., Zou H., Wang B., Sun Q., Fu A., Wang Y., Wang Y., Xu X., Li W. Probiotic Bacillus amyloliquefaciens SC06 induces autophagy to protect against pathogens in macrophages. Front. Microbiol. 2017;8:469.
Not in our library10.3389/fmicb.2017.00469
218.
Chiu H.C., Kulp S.K., Soni S., Wang D., Gunn J.S., Schlesinger L.S., Chen C.S. Eradication of intracellular Salmonella enterica serovar Typhimurium with a small-molecule, host cell-directed agent. Antimicrob. Agents Chemother. 2009;53:5236-5244.
Not in our library10.1128/aac.00555-09
219.
Chiu H.C., Soni S., Kulp S.K., Curry H., Wang D., Gunn J.S., Schlesinger L.S., Chen C.S. Eradication of intracellular Francisella tularensis in THP-1 human macrophages with a novel autophagy inducing agent. J. Biomed. Sci. 2009;16:110.
Not in our library10.1186/1423-0127-16-110
220.
Vitamin D Inhibits Human Immunodeficiency Virus Type 1 and Mycobacterium tuberculosis Infection in Macrophages through the Induction of Autophagy · 2012
No notice
221.
Steele S., Brunton J., Kawula T. The role of autophagy in intracellular pathogen nutrient acquisition. Front. Cell. Infect. Microbiol. 2015;5:51.
Not in our library10.3389/fcimb.2015.00051
222.
Niu H., Xiong Q., Yamamoto A., Hayashi-Nishino M., Rikihisa Y. Autophagosomes induced by a bacterial Beclin 1 binding protein facilitate obligatory intracellular infection. Proc. Natl. Acad. Sci. USA. 2012;109:20800-20807.
Not in our library10.1073/pnas.1218674109
223.
Niu H., Yamaguchi M., Rikihisa Y. Subversion of cellular autophagy by Anaplasma phagocytophilum. Cell. Microbiol. 2008;10:593-605.
Not in our library10.1111/j.1462-5822.2007.01068.x
224.
Moreau K., Lacas-Gervais S., Fujita N., Sebbane F., Yoshimori T., Simonet M., Lafont F. Autophagosomes can support Yersinia pseudotuberculosis replication in macrophages. Cell. Microbiol. 2010;12:1108-1123.
Not in our library10.1111/j.1462-5822.2010.01456.x
225.
Host Response during Yersinia pestis Infection of Human Bronchial Epithelial Cells Involves Negative Regulation of Autophagy and Suggests a Modulation of Survival-Related and Cellular Growth Pathways · 2015
Not checked
226.
Vázquez C.L., Colombo M.I. Coxiella burnetii modulates Beclin 1 and Bcl-2, preventing host cell apoptosis to generate a persistent bacterial infection. Cell Death Differ. 2010;17:421-438.
Not in our library10.1038/cdd.2009.129
227.
Starr T., Child R., Wehrly T.D., Hansen B., Hwang S., López-Otin C., Virgin H.W., Celli J. Selective subversion of autophagy complexes facilitates completion of the Brucella intracellular cycle. Cell Host Microbe. 2012;11:33-45.
Not in our library10.1016/j.chom.2011.12.002
228.
Dorn B.R., Dunn W.A., Progulske-Fox A. Bacterial interactions with the autophagic pathway. Cell. Microbiol. 2002;4:1-10.
Not in our library10.1046/j.1462-5822.2002.00164.x
229.
Mariño G., López-Otín C. Autophagy: Molecular mechanisms, physiological functions and relevance in human pathology. Cell. Mol. Life Sci. 2004;61:1439-1454.
Not in our library10.1007/s00018-004-4012-4
230.
Klein J.A., Powers T.R., Knodler L.A. Measurement of Salmonella enterica internalization and vacuole lysis in epithelial cells. Methods Mol. Biol. 2017;1519:285-296.
Not in our library10.1007/978-1-4939-6581-6_19
231.
Salmonella Typhimurium disrupts Sirt1/AMPK checkpoint control of mTOR to impair autophagy · 2017
No notice
232.
De Andrade Silva B.J., de Mattos Barbosa M.G., Andrade P.R., Ferreira H., da Costa Nery J.A., Coˆrte-Real S., da Silva G.M.S., Rosa P.S., Fabri M., Sarno E.N., et al. Autophagy is an innate mechanism associated with leprosy polarization. PLoS Pathog. 2017;13:e1006103.
Not in our library10.1371/journal.ppat.1006103
233.
Deretic V. Multiple regulatory and effector roles of autophagy in immunity. Curr. Opin. Immunol. 2009;21:53-62.
Not in our library10.1016/j.coi.2009.02.002
234.
Kudchodkar S.B., Levine B. Viruses and autophagy. Rev. Med. Virol. 2009;19:359-378.
Not in our library10.1002/rmv.630
235.
Paul P., Münz C. Autophagy and mammalian viruses: Roles in immune response, viral replication, and beyond. Adv. Virus Res. 2016;95:149-195.
Not in our library10.1016/bs.aivir.2016.02.002
236.
English L., Chemali M., Duron J., Rondeau C., Laplante A., Gingras D., Alexander D., Leib D., Norbury C., Lippé R. Autophagy enhances the presentation of endogenous viral antigens on MHC class I molecules during HSV-1 infection. Nat. Immunol. 2009;10:480-487.
Not in our library10.1038/ni.1720
237.
Nimmerjahn F., Milosevic S., Behrends U., Jaffee E.M., Pardoll D.M., Bornkamm G.W., Mautner J. Major Histocompatibility complex class ii-restricted presentation of a cytosolic antigen by autophagy. Eur. J. Immunol. 2003;33:1250-1259.
Not in our library10.1002/eji.200323730
238.
Schmid D., Pypaert M., Münz C. Antigen-loading compartments for major histocompatibility complex class II molecules continuously receive input from autophagosomes. Immunity. 2007;26:79-92.
Not in our library10.1016/j.immuni.2006.10.018
239.
Shelly S., Lukinova N., Bambina S., Berman A., Cherry S. Autophagy is an essential component of Drosophila immunity against vesicular stomatitis virus. Immunity. 2009;30:588-598.
Not in our library10.1016/j.immuni.2009.02.009
240.
Nakamoto M., Moy R.H., Xu J., Bambina S., Yasunaga A., Shelly S.S., Gold B., Cherry S. Virus recognition by Toll-7 activates antiviral autophagy in Drosophila. Immunity. 2012;36:658-667.
Not in our library10.1016/j.immuni.2012.03.003
241.
Moy R.H., Gold B., Molleston J.M., Schad V., Yanger K., Salzano M.V., Yagi Y., Fitzgerald K.A., Stanger B.Z., Soldan S.S. Antiviral autophagy restricts rift valley fever virus infection and is conserved from flies to mammals. Immunity. 2014;40:51-65.
Not in our library10.1016/j.immuni.2013.10.020
242.
Owczarczyk A.B., Schaller M.A., Reed M., Rasky A.J., Lombard D.B., Lukacs N.W. Sirtuin 1 regulates dendritic cell activation and autophagy during respiratory syncytial virus–induced immune responses. J Immunol. 2015;195:1637-1646.
Not in our library10.4049/jimmunol.1500326
243.
Needs S., Kaas S., Horne T., Alonzi D., Allman S. Stimulation of autophagy by salicylamide derivatives-implications for viral infection. Proceedings of the Frankfurt Conference on Ubiquitin and Autophagy “Quality Control in life Process”.
Not in our library
244.
Fan X., Han S., Yan D., Gao Y., Wei Y., Liu X., Liao Y., Guo H., Sun S. Foot-and-mouth disease virus infection suppresses autophagy and NF-κB antiviral responses via degradation of ATG5-ATG12 by 3Cpro. Cell Death Dis. 2017;8:e2561.
Not in our library10.1038/cddis.2016.489
245.
Shintani T., Klionsky D.J. Autophagy in health and disease: A double-edged sword. Science. 2004;306:990-995.
Not in our library10.1126/science.1099993
246.
Li C., Fu X., Lin Q., Liu L., Liang H., Huang Z., Li N. Autophagy promoted infectious kidney and spleen necrosis virus replication and decreased infectious virus yields in CPB cell line. Fish Shellfish Immunol. 2017;60:25-32.
Not in our library10.1016/j.fsi.2016.11.037
247.
Reggiori F., Monastyrska I., Verheije M.H., Calì T., Ulasli M., Bianchi S., Bernasconi R., De Haan C.A., Molinari M. Coronaviruses hijack the LC3-I-positive EDEMosomes, ER-derived vesicles exporting short-lived ERAD regulators, for replication. Cell Host Microbe. 2010;7:500-508.
Not in our library10.1016/j.chom.2010.05.013
248.
Wong J., Zhang J., Si X., Gao G., Mao I., Mcmanus B.M., Luo H. Autophagosome supports coxsackievirus B3 replication in host cells. J. Virol. 2008;82:9143-9153.
Not in our library10.1128/jvi.00641-08
249.
Taylor M.P., Kirkegaard K. Modification of cellular autophagy protein LC3 by poliovirus. J. Virol. 2007;81:12543-12553.
Not in our library10.1128/jvi.00755-07
250.
Chen W.L., Choi J., Wakita T., Yen T., Ou J.H.J. Induction of incomplete autophagic response by hepatitis C virus via the unfolded protein response. Hepatology. 2008;48:1054-1061.
Not in our library10.1002/hep.22464
251.
Ke P.Y., Chen S.S.L. Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro. J. Clin. Investig. 2011;121:37-56.
Not in our library10.1172/jci41474
252.
Shrivastava S., Raychoudhuri A., Steele R., Ray R., Ray R.B. Knockdown of autophagy enhances the innate immune response in hepatitis C virus–infected hepatocytes. Hepatology. 2011;53:406-414.
Not in our library10.1002/hep.24073
253.
Gannagé M., Dormann D., Albrecht R., Dengjel J., Torossi T., Rämer P.C., Lee M., Strowig T., Arrey F., Conenello G., et al. Matrix protein 2 of influenza A virus blocks autophagosome fusion with lysosomes. Cell Host Microbe. 2009;6:367-380.
Not in our library10.1016/j.chom.2009.09.005
254.
Rossman J.S., Lamb R.A. Autophagy, apoptosis, and the influenza virus M2 protein. Cell Host Microbe. 2009;6:299-300.
Not in our library10.1016/j.chom.2009.09.009
255.
Zhou Z., Jiang X., Liu D., Fan Z., Hu X., Yan J., Wang M., Gao G.F. Autophagy is involved in influenza a virus replication. Autophagy. 2009;5:321-328.
Not in our library10.4161/auto.5.3.7406
256.
Pissawong T., Maneewatch S., Thueng-in K., Srimanote P., Dong-din-on F., Thanongsaksrikul J., Songserm T., Tongtawe P., Bangphoomi K., Chaicumpa W. Human monoclonal ScFv that bind to different functional domains of M2 and inhibit H5N1 influenza virus replication. Virol. J. 2013;10:148.
Not in our library10.1186/1743-422x-10-148
257.
Hansen M.D., Johnsen I.B., Stiberg K.A., Sherstova T., Wakita T., Richard G.M., Kandasamy R.K., Meurs E.F., Anthonsen M.W. Hepatitis C virus triggers Golgi fragmentation and autophagy through the immunity-related GTPase M. Proc. Natl. Acad. Sci. USA. 2017;114:E3462-E3471.
Not in our library10.1073/pnas.1616683114
258.
Meng C., Zhou Z., Jiang K., Yu S., Jia L., Wu Y., Liu Y., Meng S., Ding C. Newcastle disease virus triggers autophagy in U251 glioma cells to enhance virus replication. Arch. Virol. 2012;157:1011-1018.
Not in our library10.1007/s00705-012-1270-6
259.
Sun Y., Yu S., Ding N., Meng C., Meng S., Zhang S., Zhan Y., Qiu X., Tan L., Chen H. Autophagy benefits the replication of Newcastle disease virus in chicken cells and tissues. J. Virol. 2014;88:525-537.
Not in our library10.1128/jvi.01849-13
260.
Zhou D., Spector S.A. Human immunodeficiency virus type-1 infection inhibits autophagy. AIDS. 2008;22:695-699.
Not in our library10.1097/qad.0b013e3282f4a836
261.
Kyei G.B., Dinkins C., Davis A.S., Roberts E., Singh S.B., Dong C., Wu L., Kominami E., Ueno T., Yamamoto A. Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages. J. Cell Biol. 2009;186:255-268.
Not in our library10.1083/jcb.200903070
262.
Saribas A.S., Khalili K., Sariyer I.K. Dysregulation of autophagy by HIV-1 Nef in human astrocytes. Cell Cycle. 2015;14:2899-2904.
Not in our library10.1080/15384101.2015.1069927
263.
Zhou H.Y., Zheng Y.H., He Y., Chen Z., He B. The role of autophagy in THP-1 macrophages resistance to HIV-vpr-induced apoptosis. Exp. Cell Res. 2017;351:68-73.
Not in our library10.1016/j.yexcr.2016.12.024
264.
Taylor G.S., Mautner J., Münz C. Autophagy in herpesvirus immune control and immune escape. Herpesviridae. 2011;2:2.
Not in our library10.1186/2042-4280-2-2
265.
Liang Q., Chang B., Brulois K.F., Castro K., Min C.K., Rodgers M.A., Shi M., Ge J., Feng P., Oh B.H., et al. Kaposi’s sarcoma-associated herpesvirus K7 modulates Rubicon-mediated inhibition of autophagosome maturation. J. Virol. 2013;87:12499-12503.
Not in our library10.1128/jvi.01898-13
266.
Su M., Mei Y., Sanishvili R., Levine B., Colbert C.L., Sinha S. Targeting γ-herpesvirus 68 Bcl-2-ediated down-regulation of autophagy. J. Biol. Chem. 2014;289:8029-8040.
Not in our library10.1074/jbc.m113.515361
267.
Intracellular Vesicle Acidification Promotes Maturation of Infectious Poliovirus Particles · 2012
No notice
268.
Li X., Gong Z., Zhang L., Zhao C., Zhao X., Gu X., Chen H. Autophagy knocked down by high-risk HPV infection and uterine cervical carcinogenesis. Int. J. Clin. Exp. Med. 2015;8:10304.
Not in our library
269.
Mclean J.E., Wudzinska A., Datan E., Quaglino D., Zakeri Z. Flavivirus NS4A-induced autophagy protects cells against death and enhances virus replication. J. Biol. Chem. 2011;286:22147-22159.
Not in our library10.1074/jbc.m110.192500
270.
Maier H.J., Britton P. Involvement of autophagy in coronavirus replication. Viruses. 2012;4:3440-3451.
Not in our library10.3390/v4123440
271.
Cottam E.M., Maier H.J., Manifava M., Vaux L.C., Chandra-Schoenfelder P., Gerner W., Britton P., Ktistakis N.T., Wileman T. Coronavirus Nsp6 proteins generate autophagosomes from the endoplasmic reticulum via an omegasome intermediate. Autophagy. 2011;7:1335-1347.
Not in our library10.4161/auto.7.11.16642
272.
O’donnell V., Pacheco J.M., Larocco M., Burrage T., Jackson W., Rodriguez L.L., Borca M.V., Baxt B. Foot-and-mouth disease virus utilizes an autophagic pathway during viral replication. Virology. 2011;410:142-150.
Not in our library10.1016/j.virol.2010.10.042
273.
Shrivastava S., Devhare P., Sujijantarat N., Steele R., Kwon Y.C., Ray R., Ray R.B. Knockdown of autophagy inhibits infectious hepatitis C virus release by the exosomal pathway. J. Virol. 2016;90:1387-1396.
Not in our library10.1128/jvi.02383-15
274.
Dash S., Chava S., Aydin Y., Chandra P.K., Ferraris P., Chen W., Balart L.A., Wu T., Garry R.F. Hepatitis C virus infection induces autophagy as a prosurvival mechanism to alleviate hepatic ER-stress response. Viruses. 2016;8:150.
Not in our library10.3390/v8050150
275.
Huang X., Yue Y., Li D., Zhao Y., Qiu L., Chen J., Pan Y., Xi J., Wang X., Sun Q. Antibody-dependent enhancement of dengue virus infection inhibits rlr-mediated type-1 IFN-independent signalling through upregulation of cellular autophagy. Sci. Rep. 2016;6:22303.
Not in our library10.1038/srep22303
276.
Wang Y., Duan Y., Han C., Yao S., Qi X., Gao Y., Maier H.J., Britton P., Chen L., Zhang L., et al. Infectious bursal disease virus subverts autophagic vacuoles to promote viral maturation and release. J. Virol. 2017;91:e01883-16.
Not in our library10.1128/jvi.01883-16
277.
Jiang H., White E.J., Gomez-Manzano C., Fueyo J. Adenovirus’s last trick: You say lysis, we say autophagy. Autophagy. 2008;4:118-120.
Not in our library10.4161/auto.5260
278.
Levine B., Deretic V. Unveiling the roles of autophagy in innate and adaptive immunity. Nat. Rev. Immunol. 2007;7:767-777.
Not in our library10.1038/nri2161
279.
Tang H., Da L., Mao Y., Li Y., Li D., Xu Z., Li F., Wang Y., Tiollais P., Li T. Hepatitis B virus X protein sensitizes cells to starvation-induced autophagy via up-regulation of beclin 1 expression. Hepatology. 2009;49:60-71.
Not in our library10.1002/hep.22581
280.
Park S., Buck M.D., Desai C., Zhang X., Loginicheva E., Martinez J., Freeman M.L., Saitoh T., Akira S., Guan J.L. Autophagy genes enhance murine gamma herpesvirus 68 reactivation from latency by preventing virus-induced systemic inflammation. Cell Host Microbe. 2016;19:91-101.
Not in our library10.1016/j.chom.2015.12.010
281.
Orvedahl A., Alexander D., Talloczy Z., Burns D., Leib D.A., Levine B. HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein. Cell Host Microbe. 2007;1:23-35.
Not in our library10.1016/j.chom.2006.12.001
282.
Sun Y., Li C., Shu Y., Ju X., Zou Z., Wang H., Rao S., Guo F., Liu H., Nan W., et al. Inhibition of autophagy ameliorates acute lung injury caused by avian influenza A H5N1 infection. Sci. Signal. 2012;5:Ra16.
Not in our library10.1126/scisignal.2001931
283.
Surviladze Z., Sterk R.T., Deharo S.A., Ozbun M.A. Cellular entry of human papillomavirus type 16 involves activation of the phosphatidylinositol 3-kinase/akt/mtor pathway and inhibition of autophagy. J Virol. 2013;87:2508-2517.
Not in our library10.1128/jvi.02319-12
284.
Coronavirus Replication Complex Formation Utilizes Components of Cellular Autophagy · 2004
No notice
285.
Choi A.M., Ryter S.W., Levine B. Autophagy in human health and disease. N. Engl. J. Med. 2013;368:651-662.
Not in our library10.1056/nejmra1205406
286.
Liang X.H., Jackson S., Seaman M., Brown K., Kempkes B., Hibshoosh H., Levine B. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature. 1999;402:672-676.
Not in our library10.1038/45257
287.
Autophagy Modulation in Cancer: Current Knowledge on Action and Therapy · 2018
No notice
288.
Tang D., Kang R., Livesey K.M., Cheh C.W., Farkas A., Loughran P., Hoppe G., Bianchi M.E., Tracey K.J., Zeh H.J., et al. Endogenous HMGB1 regulates autophagy. J. Cell Biol. 2010;190:881-892.
Not in our library10.1083/jcb.200911078
289.
Qu X., Yu J., Bhagat G., Furuya N., Hibshoosh H., Troxel A., Rosen J., Eskelinen E.L., Mizushima N., Ohsumi Y., et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J. Clin. Investig. 2003;112:1809-1820.
Not in our library10.1172/jci20039
290.
Komatsu M., Waguri S., Koike M., Sou Y.S., Ueno T., Hara T., Mizushima N., Iwata J., Ezaki J., Murata S., et al. Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell. 2007;131:1149-1163.
Not in our library10.1016/j.cell.2007.10.035
291.
Takamura A., Komatsu M., Hara T., Sakamoto A., Kishi C., Waguri S., Eishi Y., Hino O., Tanaka K., Mizushima N. Autophagy-deficient mice develop multiple liver tumors. Genes Dev. 2011;25:795-800.
Not in our library10.1101/gad.2016211
292.
Levine B. Cell biology, autophagy and cancer. Nature. 2007;446:745-747.
Not in our library10.1038/446745a
293.
Yue Z., Jin S., Yang C., Levine A.J., Heintz N. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc. Natl. Acad. Sci. USA. 2003;100:15077-15082.
Not in our library10.1073/pnas.2436255100
294.
Gu Y., Chen T., Li G., Xu C., Xu Z., Zhang J., He K., Zheng L., Guan Z., Su X., et al. Lower Beclin 1 downregulates HER2 expression to enhance tamoxifen sensitivity and predicts a favorable outcome for ER positive breast cancer. Oncotarget. 2016;8:52156-52177.
Not in our library10.18632/oncotarget.11044
295.
Liang C., Feng P., Ku B., Dotan I., Canaani D., Oh B.H., Jung J.U. Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG. Nat. Cell Biol. 2006;8:688-699.
Not in our library10.1038/ncb1426
296.
Jin S. Autophagy, mitochondrial quality control, and oncogenesis. Autophagy. 2006;2:80-84.
Not in our library10.4161/auto.2.2.2460
297.
Degenhardt K., Mathew R., Beaudoin B., Bray K., Anderson D., Chen G., Mukherjee C., Shi Y., Gélinas C., Fan Y., et al. Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell. 2006;10:51-64.
Not in our library10.1016/j.ccr.2006.06.001
298.
Mathew R., Kongara S., Beaudoin B., Karp C.M., Bray K., Degenhardt K., Chen G., Jin S., White E. Autophagy suppresses tumor progression by limiting chromosomal instability. Genes Dev. 2007;21:1367-1381.
Not in our library10.1101/gad.1545107
299.
Cargnello M., Tcherkezian J., Roux P.P. The expanding role of mTOR in cancer cell growth and proliferation. Mutagenesis. 2015;30:169-176.
Not in our library10.1093/mutage/geu045
300.
Ravikumar B., Vacher C., Berger Z., Davies J.E., Luo S., Oroz L.G., Scaravilli F., Easton D.F., Duden R., O’Kane C.J., et al. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet. 2004;36:585-595.
Not in our library10.1038/ng1362
301.
Feng Z., Zhang H., Levine A.J., Jin S. The coordinate regulation of the p53 and mTOR pathways in cells. Proc. Natl. Acad. Sci. USA. 2005;102:8204-8209.
Not in our library10.1073/pnas.0502857102
302.
Tsuchihara K., Fujii S., Esumi H. Autophagy and cancer, dynamism of the metabolism of tumor cells and tissues. Cancer Lett. 2009;278:130-138.
Not in our library10.1016/j.canlet.2008.09.040
303.
Cao Z.X., Yang Y.T., Yu S., Li Y.Z., Wang W.W., Huang J., Xie X.F., Xiong L., Lei S., Peng C. Pogostone induces autophagy and apoptosis involving PI3K/Akt/mTOR axis in human colorectal carcinoma HCT116 cells. J. Ethnopharmacol. 2017;202:20-27.
Not in our library10.1016/j.jep.2016.07.028
304.
Cerezo M., Rocchi S. New anti-cancer molecules targeting HSPA5/BIP to induce endoplasmic reticulum stress, autophagy and apoptosis. Autophagy. 2017;13:216-217.
Not in our library10.1080/15548627.2016.1246107
305.
Cao C., Qi H., Chen F., He J. Trichosanthin inhibits human ovarian cancer cells growth due to apoptosis and autophagy. Int. J. Clin. Exp. Med. 2017;10:5497-5503.
Not in our library
306.
Sato K., Tsuchihara K., Fujii S., Sugiyama M., Goya T., Atomi Y., Ueno T., Ochiai A., Esumi H. Autophagy is activated in colorectal cancer cells and contributes to the tolerance to nutrient deprivation. Cancer Res. 2007;67:9677-9684.
Not in our library10.1158/0008-5472.can-07-1462
307.
Ogier-Denis E., Houri J.J., Bauvy C., Codogno P. Guanine nucleotide exchange on heterotrimeric Gi3 protein controls autophagic sequestration in HT-29 cells. J. Biol. Chem. 1996;271:28593-28600.
Not in our library10.1074/jbc.271.45.28593
308.
Schonewolf C.A., Mehta M., Schiff D., Wu H., Haffty B.G., Karantza V., Jabbour S.K. Autophagy inhibition by chloroquine sensitizes HT-29 colorectal cancer cells to concurrent chemoradiation. World J. Gastrointest Oncol. 2014;6:74-82.
Not in our library10.4251/wjgo.v6.i3.74
309.
Lee S.H., Jeong E.G., Yoo N.J., Lee S.H. Mutational and expressional analysis of BNIP3, a pro-apoptotic Bcl-2 member, in gastric carcinomas. APMIS. 2007;115:1274-1280.
Not in our library10.1111/j.1600-0643.2007.00795.x
310.
Tylichová Z., Straková N., Vondráček J., Vaculová A.H., Kozubík A., Hofmanová J. Activation of autophagy and PPARγ protect colon cancer cells against apoptosis induced by interactive effects of butyrate and DHA in a cell type-dependent manner: The role of cell differentiation. J. Nutr. Biochem. 2017;39:145-155.
Not in our library10.1016/j.jnutbio.2016.09.006
311.
Sala F.S., Ebbinghaus M., Muley V.Y., Zhou Z., Al-Saadi K.R., Pacyna-Gengelbach M., O’Sullivan G.A., Betz H., König R., Wang Z.Q., et al. Tumor suppression in mice lacking GABARAP, an Atg8/LC3 family member implicated in autophagy, is associated with alterations in cytokine secretion and cell death. Cell Death Dis. 2016;7:e2205.
Not in our library10.1038/cddis.2016.93
312.
Guo J.Y., Chen H.Y., Mathew R., Fan J., Strohecker A.M., Karsli-Uzunbas G. Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes Dev. 2011;25:460-470.
Not in our library10.1101/gad.2016311
313.
Janku F., McConkey D.J., Hong D.S., Kurzrock R. Autophagy as a target for anticancer therapy. Nat. Rev. Clin. Oncol. 2011;8:528-539.
Not in our library10.1038/nrclinonc.2011.71
314.
Lu Z., Luo R.Z., Lu Y., Zhang X., Yu Q., Khare S., Kondo S., Kondo Y., Yu Y., Mills G.B., et al. The tumor suppressor gene ARHI regulates autophagy and tumor dormancy in human ovarian cancer cells. J. Clin. Investig. 2008;118:3917-3929.
Not in our library10.1172/jci35512
315.
White E., Karp C., Strohecker A.M., Guo Y., Mathew R. Role of autophagy in suppression of inflammation and cancer. Curr. Opin. Cell Biol. 2010;22:212-217.
Not in our library10.1016/j.ceb.2009.12.008
316.
Gewirtz D.A. Autophagy, senescence and tumor dormancy in cancer therapy. Autophagy. 2009;5:1232-1234.
Not in our library10.4161/auto.5.8.9896
317.
Young A.R., Narita M., Ferreira M., Kirschner K., Sadaie M., Darot J.F., Tavaré S., Arakawa S., Shimizu S., Watt F.M., et al. Autophagy mediates the mitotic senescence transition. Genes Dev. 2009;23:798-803.
Not in our library10.1101/gad.519709
318.
Luo T., Fu J., Xu A., Su B., Ren Y., Li N., Zhu J., Zhao X., Dai R., Cao J., et al. PSMD10/Gankyrin induces autophagy to promote tumor progression through cytoplasmic interaction with ATG7 and nuclear transactivation of ATG7 expression. Autophagy. 2016;12:1355-1371.
Not in our library10.1080/15548627.2015.1034405
319.
Hara T., Nakamura K., Matsui M., Yamamoto A., Nakahara Y., Suzuki-Migishima R., Yokoyama M., Mishima K., Saito I., Okano H., et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature. 2006;441:885-889.
Not in our library10.1038/nature04724
320.
Simonsen A., Cumming R.C., Brech A., Isakson P., Schubert D.R., Finley K.D. Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila. Autophagy. 2008;4:176-184.
Not in our library10.4161/auto.5269
321.
Viscomi M.T., D’Amelio M., Nobili A., Cavallucci V., Latini L., Bisicchia E., Sasso V., Molinari M. Autophagy mechanisms for brain recovery. Keep it clean, keep it alive. Neurobiological and Psychological Aspects of Brain Recovery. 2017;35-53.
Not in our library
322.
Girault V., Gilard V., Marguet F., Lesueur C., Hauchecorne M., Ramdani Y., Laquerrière A., Marret S., Jégou S., Gonzalez B.J., et al. Prenatal alcohol exposure impairs autophagy in neonatal brain cortical microvessels. Cell Death Dis. 2017;8:e2610.
Not in our library10.1038/cddis.2017.29
323.
Autophagy regulates Notch degradation and modulates stem cell development and neurogenesis · 2016
No notice
324.
Nixon R.A., Yang D.S., Lee J.H. Neurodegenerative lysosomal disorders: A continuum from development to late age. Autophagy. 2008;4:590-599.
Not in our library10.4161/auto.6259
325.
Tooze S.A., Schiavo G. Liaisons dangereuses, autophagy, neuronal survival and neurodegeneration. Curr. Opin. Neurobiol. 2008;18:504-515.
Not in our library10.1016/j.conb.2008.09.015
326.
Wong E., Cuervo A.M. Autophagy gone awry in neurodegenerative diseases. Nat. Neurosci. 2010;13:805-811.
Not in our library10.1038/nn.2575
327.
Sahni S., Merlot A.M., Krishan S., Jansson P.J., Richardson D.R. Gene of the month: BECN1. J. Clin. Pathol. 2014;67:656-660.
Not in our library10.1136/jclinpath-2014-202356
328.
Lim Y., Cho H., Kim E.K. Brain metabolism as a modulator of autophagy in neurodegeneration. Brain Res. 2016;1649:158-165.
Not in our library10.1016/j.brainres.2016.02.049
329.
Nixon R.A., Cataldo A.M. Lysosomal system pathways, genes to neurodegeneration in Alzheimer’s disease. J. Alzheimers Dis. 2006;9:277-289.
Not in our library10.3233/jad-2006-9s331
330.
Pickford F., Masliah E., Britschgi M., Lucin K., Narasimhan R., Jaeger P.A., Small S., Spencer B., Rockenstein E., Levine B., et al. The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice. J. Clin. Investig. 2008;118:2190-2199.
Not in our library10.1172/jci33585
331.
Vogiatzi T., Xilouri M., Vekrellis K., Stefanis L. Wild type alpha-synuclein is degraded by chaperone-mediated autophagy and macroautophagy in neuronal cells. J. Biol. Chem. 2008;283:23542-23556.
Not in our library10.1074/jbc.m801992200
332.
Yang Q., She H., Gearing M., Colla E., Lee M., Shacka J.J., Mao Z. Regulation of neuronal survival factor MEF2D by chaperone-mediated autophagy. Science. 2009;323:124-127.
Not in our library10.1126/science.1166088
333.
Sarkar S., Davies J.E., Huang Z., Tunnacliffe A., Rubinsztein D.C. Trehalose, a novel mTOR-independent autophagy enhancer accelerates the clearance of mutant huntingtin and alphasynuclein. J. Biol. Chem. 2007;282:5641-5652.
Not in our library10.1074/jbc.m609532200
334.
Komatsu M., Waguri S., Chiba T., Murata S., Iwata J., Tanida I., Ueno T., Koike M., Uchiyama Y., Kominami E., et al. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature. 2006;441:880-884.
Not in our library10.1038/nature04723
335.
Fimia G.M., Stoykova A., Romagnoli A., Giunta L., Di Bartolomeo S., Nardacci R., Corazzari M., Fuoco C., Ucar A., Schwartz P., et al. Ambra1 regulates autophagy and development of the nervous system. Nature. 2007;447:1121-1125.
Not in our library10.1038/nature05925
336.
Webb J.L., Ravikumar B., Atkins J., Skepper J.N., Rubinsztein D.C. Alpha synuclein is degraded by both autophagy and the proteasome. J. Biol. Chem. 2003;278:25009-25013.
Not in our library10.1074/jbc.m300227200
337.
Spencer B., Potkar R., Trejo M., Rockenstein E., Patrick C., Gindi R., Adame A., Wyss- Coray T., Masliah E. Beclin 1 gene transfer activates autophagy and ameliorates the neurodegenerative pathology in alpha-synuclein models of Parkinson’s and Lewy body diseases. J. Neurosci. 2009;29:13578-13588.
Not in our library10.1523/jneurosci.4390-09.2009
338.
Dahmene M., Bérard M., Oueslati A. Dissecting the molecular pathway involved in PLK2 kinase-mediated α-synuclein-selective autophagic degradation. J. Biol. Chem. 2017;292:3919-3928.
Not in our library10.1074/jbc.m116.759373
339.
Whitworth A.J., Pallanck L.J. PINK1/Parkin mitophagy and neurodegeneration—What do we really know in vivo? Curr. Opin. Genet. Dev. 2017;44:47-53.
Not in our library10.1016/j.gde.2017.01.016
340.
Cesari R., Martin E.S., Calin G.A., Pentimalli F., Bichi R., McAdams H., Trapasso F., Drusco A., Shimizu M., Masciullo V., et al. Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25-q27. Proc. Natl. Acad. Sci. USA. 2003;100:5956-5961.
Not in our library10.1073/pnas.0931262100
341.
Vives-Bauza C., Zhou C., Huang Y., Cui M., de Vries R.L., Kim J., May J., Tocilescu M.A., Liu W., Ko H.S., et al. PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc. Natl. Acad. Sci. USA. 2010;107:378-383.
Not in our library10.1073/pnas.0911187107
342.
Jia K., Hart A.C., Levine B. Autophagy genes protect against disease caused by polyglutamine expansion proteins in Caenorhabditis elegans. Autophagy. 2007;3:21-25.
Not in our library10.4161/auto.3528
343.
Kovács T., Billes V., Komlós M., Hotzi B., Manzéger A., Tarnóci A., Papp D., Szikszai F., Szinyákovics J., Rácz A., et al. The small molecule AUTEN-99 (autophagy enhancer-99) prevents the progression of neurodegenerative symptoms. Sci. Rep. 2017;7:42014.
Not in our library10.1038/srep42014
344.
Bi X., Liao G. Autophagic-lysosomal dysfunction and neurodegeneration in Niemann-Pick type C mice: Lipid starvation or indigestion? Autophagy. 2007;3:646-648.
Not in our library10.4161/auto.5074
345.
Zhou X.J., Zhang H. Autophagy in immunity, implications in etiology of autoimmunity/autoinflammatory diseases. Autophagy. 2012;8:1286-1299.
Not in our library10.4161/auto.21212
346.
Wu D.J., Adamopoulos I.E. Autophagy and autoimmunity. Clin. Immunol. 2017;176:55-62.
Not in our library10.1016/j.clim.2017.01.007
347.
Jang Y.J., Kim J.H., Byun S. Modulation of autophagy for controlling immunity. Cells. 2019;8:138.
Not in our library10.3390/cells8020138
348.
Arnold J., Murera D., Arbogast F., Fauny J.D., Muller S., Gros F. Autophagy is dispensable for B-cell development but essential for humoral autoimmune responses. Cell Death Differ. 2016;23:853-864.
Not in our library10.1038/cdd.2015.149
349.
Germic N., Frangez Z., Yousefi S., Simon H.U. Regulation of the innate immune system by autophagy: Neutrophils, eosinophils, mast cells, NK cells. Cell Death Differ. 2019;26:703-714.
Not in our library10.1038/s41418-019-0295-8
350.
Germic N., Frangez Z., Yousefi S., Simon H.U. Regulation of the innate immune system by autophagy: Monocytes, macrophages, dendritic cells and antigen presentation. Cell Death Differ. 2019;26:715-727.
Not in our library10.1038/s41418-019-0297-6
351.
Clarke A.J., Simon A.K. Autophagy in the renewal, differentiation and homeostasis of immune cells. Nat. Rev. Immunol. 2019;19:170-183.
Not in our library10.1038/s41577-018-0095-2
352.
Sandoval H., Kodali S., Wang J. Regulation of B cell fate, survival, and function by mitochondria and autophagy. Mitochondrion. 2018;41:58-65.
Not in our library10.1016/j.mito.2017.11.005
353.
Pengo N., Scolari M., Oliva L., Milan E., Mainoldi F., Raimondi A., Fagioli C., Merlini A., Mariani E., Pasqualetto E., et al. Plasma cells require autophagy for sustainable immunoglobulin production. Nat. Immunol. 2013;14:298-305.
Not in our library10.1038/ni.2524
354.
Paul S., Kashyap A.K., Jia W., He Y.W., Schaefer B.C. Selective autophagy of the adaptor protein Bcl10 modulates T cell receptor activation of NF-κB. Immunity. 2012;36:947-958.
Not in our library10.1016/j.immuni.2012.04.008
355.
Zhong Z., Umemura A., Sanchez-Lopez E., Liang S., Shalapour S., Wong J., He F., Boassa D., Perkins G., Ali S.R., et al. NF-κB restricts inflammasome activation via elimination of damaged mitochondria. Cell. 2016;164:896-910.
Not in our library10.1016/j.cell.2015.12.057
356.
Harris J., Hartman M., Roche C., Zeng S.G., O’Shea A., Sharp F.A., Lambe E.M., Creagh E.M., Golenbock D.T., Tschopp J., et al. Autophagy controls IL-1beta secretion by targeting pro-IL-1beta for degradation. J. Biol. Chem. 2011;286:9587-9597.
Not in our library10.1074/jbc.m110.202911
357.
Park H.J., Lee S.J., Kim S.H., Han J., Bae J., Kim S.J., Park C.G., Chun T. IL-10 inhibits the starvation induced autophagy in macrophages via class I phosphatidylinositol 3-kinase (PI3K) pathway. Mol. Immunol. 2011;48:720-727.
Not in our library10.1016/j.molimm.2010.10.020
358.
The Therapeutic and Pathogenic Role of Autophagy in Autoimmune Diseases · 2018
No notice
359.
Allison S.J. Systemic lupus erythematosus: Defective noncanonical autophagy in SLE-like disease. Nat. Rev. Rheumatol. 2016;12:311.
Not in our library10.1038/nrrheum.2016.73
360.
AP1S3 Mutations Cause Skin Autoinflammation by Disrupting Keratinocyte Autophagy and Up-Regulating IL-36 Production · 2016
No notice
361.
Lee H.K., Lund J.M., Ramanathan B., Mizushima N., Iwasaki A. Autophagy-dependent viral recognition by plasmacytoid dendritic cells. Science. 2007;315:1398-1401.
Not in our library10.1126/science.1136880
362.
Jin J., Tu Q., Gong J., Zhao L., Liang S., He Q. Autophagy activity and expression pattern of autophagy-related markers in the podocytes of patients with lupus nephritis: Association with pathological classification. Ren. Fail. 2019;41:294-302.
Not in our library10.1080/0886022x.2019.1598432
363.
Wang F., Muller S. Manipulating autophagic processes in autoimmune diseases: A special focus on modulating chaperone-mediated autophagy, an emerging therapeutic target. Front. Immunol. 2015;6:252.
Not in our library10.3389/fimmu.2015.00252
364.
The role of autophagy induced by tumor microenvironment in different cells and stages of cancer · 2015
No notice
365.
The relationship between autophagy and the immune system and its applications for tumor immunotherapy · 2019
No notice
366.
Rothermel B.A., Hill J.A. Autophagy in load-induced heart disease. Circ. Res. 2008;103:1363-1369.
Not in our library10.1161/circresaha.108.186551
367.
Gustafsson A.B., Gottlieb R.A. Autophagy in ischemic heart disease. Circ. Res. 2009;104:150-158.
Not in our library10.1161/circresaha.108.187427
368.
Terman A., Brunk U.T. Autophagy in cardiac myocyte homeostasis, aging, and pathology. Cardiovasc. Res. 2005;68:355-365.
Not in our library10.1016/j.cardiores.2005.08.014
369.
Nakai A., Yamaguchi O., Takeda T., Higuchi Y., Hikoso S., Taniike M., Omiya S., Mizote I., Matsumura Y., Asahi M., et al. The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress. Nat. Med. 2007;13:619-624.
Not in our library10.1038/nm1574
370.
Pattison J.S., Robbins J. Autophagy and proteotoxicity in cardiomyocytes. Autophagy. 2011;7:1259-1260.
Not in our library10.4161/auto.7.10.16882
371.
Nishino I., Fu J., Tanji K., Yamada T., Shimojo S., Koori T., Mora M., Riggs J.E., Oh S.J., Koga Y., et al. Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease). Nature. 2000;406:906-910.
Not in our library10.1038/35022604
372.
Tanaka Y., Guhde G., Suter A., Eskelinen E.L., Hartmann D., Lüllmann-Rauch R., Janssen P.M., Blanz J., von Figura K., Saftig P. Accumulation of autophagic vacuoles and cardiomyopathy in LAMP-2-deficient mice. Nature. 2000;406:902-906.
Not in our library10.1038/35022595
373.
Kuma A., Hatano M., Matsui M., Yamamoto A., Nakaya H., Yoshimori T., Ohsumi Y., Tokuhisa T., Mizushima N. The role of autophagy during the early neonatal starvation period. Nature. 2004;432:1032-1036.
Not in our library10.1038/nature03029
374.
Preconditioning Involves Selective Mitophagy Mediated by Parkin and p62/SQSTM1 · 2011
No notice
375.
Takemura G., Miyata S., Kawase Y., Okada H., Maruyama R., Fujiwara H. Autophagic degeneration and death of cardiomyocytes in heart failure. Autophagy. 2006;2:212-214.
Not in our library10.4161/auto.2608
376.
Akazawa H., Komazaki S., Shimomura H., Terasaki F., Zou Y., Takano H., Nagai T., Komuro I. Diphtheria toxin-induced autophagic cardiomyocyte death plays a pathogenic role in mouse model of heart failure. J. Biol. Chem. 2004;279:41095-41103.
Not in our library10.1074/jbc.m313084200
377.
Schiattarella G.G., Hill J.A. Therapeutic targeting of autophagy in cardiovascular disease. J. Mol. Cell Cardiol. 2015;95:86-93.
Not in our library10.1016/j.yjmcc.2015.11.019
378.
Wang C., Xu W., Zhang Y., Zhang F., Huang K. PARP1 promote autophagy in cardiomyocytes via modulating FoxO3a transcription. Cell Death Dis. 2018;9:1047.
Not in our library10.1038/s41419-018-1108-6
379.
Hamaï A., Mehrpour M. Autophagy and iron homeostasis. Med. Sci. 2017;33:260-267.
Not in our library10.1051/medsci/20173303012
380.
Das T.K., Wati M.R., Fatima-Shad K. Oxidative stress gated by Fenton and Haber Weiss reactions and its association with Alzheimer’s disease. Arch. Neurosci. 2015;2:e20078.
Not in our library
381.
Donovan A., Roy C.N., Andrews N.C. The ins and outs of iron homeostasis. Physiology. 2006;21:115-123.
Not in our library10.1152/physiol.00052.2005
382.
Kurz T., Gustafsson B., Brunk U.T. Cell sensitivity to oxidative stress is influenced by ferritin autophagy. Free Radic. Biol. Med. 2011;50:1647-1658.
Not in our library10.1016/j.freeradbiomed.2011.03.014
383.
Karlsson M., Frennesson C., Gustafsson T., Brunk U.T., Nilsson S.E., Kurz T. Autophagy of iron-binding proteins may contribute to the oxidative stress resistance of ARPE-19 cells. Exp. Eye Res. 2013;116:359-365.
Not in our library10.1016/j.exer.2013.10.014
384.
Krishan S., Jansson P.J., Gutierrez E., Lane D.J., Richardson D., Sahni S. Iron metabolism and autophagy: A poorly explored relationship that has important consequences for health and disease. Nagoya J. Med. Sci. 2015;77:1-6.
Not in our library
385.
Dowdle W.E., Nyfeler B., Nagel J., Elling R.A., Liu S., Triantafellow E., Menon S., Wang Z., Honda A., Pardee G., et al. Selective vps34 inhibitor blocks autophagy and uncovers a role for ncoa4 in ferritin degradation and iron homeostasis in vivo. Nat. Cell Biol. 2014;16:1069-1079.
Not in our library10.1038/ncb3053
386.
Berndt J.D. Ironing out the details with autophagy. Sci. Signal. 2014;7:ec99.
Not in our library10.1126/scisignal.2005363
387.
Mancias J.D., Wang X., Gygi S.P., Harper J.W., Kimmelman A.C. Quantitative proteomics identifies ncoa4 as the cargo receptor mediating ferritinophagy. Nature. 2014;509:105-109.
Not in our library10.1038/nature13148
388.
Che Y., Wang Z.P., Yuan Y., Zhang N., Jin Y.G., Wan C.X., Tang Q.Z. Role of autophagy in a model of obesity: A long-term high fat diet induces cardiac dysfunction. Mol. Med. Rep. 2018;18:3251-3261.
Not in our library10.3892/mmr.2018.9301
389.
Bhattacharya D., Mukhopadhyay M., Bhattacharyya M., Karmakar P. Is autophagy associated with diabetes mellitus and its complications? A review. EXCLI J. 2018;17:709-720.
Not in our library10.17179/excli2018-1353
390.
Yang L., Li P., Fu S., Calay E.S., Hotamisligil G.S. Defective hepatic autophagy in obesity promotes ER stress and causes insulin resistance. Cell Metab. 2010;11:467-478.
Not in our library10.1016/j.cmet.2010.04.005
391.
Ebato C., Uchida T., Arakawa M., Komatsu M., Ueno T., Komiya K., Azuma K., Hirose T., Tanaka K., Kominami E., et al. Autophagy is important in islet homeostasis and compensatory increase of beta cell mass in response to high-fat diet. Cell Metab. 2008;8:325-332.
Not in our library10.1016/j.cmet.2008.08.009
392.
Jung H.S., Chung K.W., Won Kim J., Kim J., Komatsu M., Tanaka K., Nguyen Y.H., Kang T.M., Yoon K.H., Kim J.W., et al. Loss of autophagy diminishes pancreatic beta cell mass and function with resultant hyperglycemia. Cell Metab. 2008;8:318-324.
Not in our library10.1016/j.cmet.2008.08.013
393.
Arsham A.M., Neufeld T.P. A genetic screen in Drosophila reveals novel cytoprotective functions of the autophagy-lysosome pathway. PLoS ONE. 2009;4:e6068.
Not in our library10.1371/journal.pone.0006068
394.
Benhar M., Forrester M.T., Stamler J.S. Protein denitrosylation: Enzymatic mechanisms and cellular functions. Nat. Rev. Mol. Cell Biol. 2009;10:721-732.
Not in our library10.1038/nrm2764
395.
Zhang K. “NO” to autophagy: Fat does the trick for diabetes. Diabetes. 2018;67:180-181.
Not in our library10.2337/dbi17-0048
396.
Qian Q., Zhang Z., Orwig A., Chen S., Ding W.X., Xu Y., Kunz R.C., Lind N.R.L., Stamler J.S., Yang L. S-Nitrosoglutathione reductase dysfunction contributes to obesity-associated hepatic insulin resistance via regulating autophagy. Diabetes. 2018;67:193-207.
Not in our library10.2337/db17-0223
397.
Subudhi B.B., Chattopadhyay S., Mishra P., Kumar A. Current strategies for inhibition of Chikungunya infection. Viruses. 2018;10:235.
Not in our library10.3390/v10050235
398.
Franco L.H., Nair V.R., Scharn C.R., Xavier R.J., Torrealba J.R., Shiloh M.U., Levine B. The ubiquitin ligase Smurf1 functions in selective autophagy of Mycobacterium tuberculosis and anti-tuberculous host defense. Cell Host Microbe. 2017;21:59-72.
Not in our library10.1016/j.chom.2016.11.002
399.
Stige K.E., Gjerde I.O., Houge G., Knappskog P.M., Tzoulis C. Beta-propeller protein-associated neurodegeneration: A case report and review of the literature. Clin. Case Rep. 2018;6:353-362.
Not in our library10.1002/ccr3.1358
400.
Pott J., Maloy K.J. Epithelial autophagy controls chronic colitis by reducing TNF-induced apoptosis. Autophagy. 2018;14:1460-1461.
Not in our library10.1080/15548627.2018.1450021
401.
Iida T., Onodera K., Nakase H. Role of autophagy in the pathogenesis of inflammatory bowel disease. World J. Gastroenterol. 2017;23:1944-1953.
Not in our library10.3748/wjg.v23.i11.1944
402.
Gorski S.M., Qadir M.A. Inhibition of Autophagy Genes in Cancer Chemotherapy. U.S. Patent. 2011.
Not in our library
403.
Amaravadi R.K., Winkler J. Dimeric Quinacrine Derivatives as Autophagy Inhibitors for Cancer Therapy. Patent. 2016.
Not in our library
404.
Xu H., Zhang H., Lao Y., Wang X., Chen K., Yang D., Chen S., Lin C., Bian Z., Lu A., et al. Anti-Cervical Cancer Compound and Method of Use Thereof. U.S. Patent. 2016.
Not in our library
405.
Carew J., Phillips J.G. Substituted Thioxanthenone Autophagy Inhibitors. U.S. Patent. 2018.
Not in our library
406.
Law Y.K., Wu A.G., Wong K.W., Liu L. Autophagy enhancer for treatment of neurodegenerative diseases. U.S. Patent. 2015.
Not in our library
407.
D’amelio M., Molinari M., Viscomi M.T., Cecconi F. Autophagy Enhancing Compounds, Peptides and Peptidomimetic Compounds for Use in the Treatment of Neuronal Diseases. Patent. 2012.
Not in our library
408.
Jung J.U., Lee J.S. Highly Potent Peptides to Control Cancer and Neurodegenerative Diseases. Patent. 2010.
Not in our library
409.
Middleton R.P., Zanghi B.M. Methods for Reducing Neurodegeneration. Patent. 2016.
Not in our library
410.
Bradner J.E., Shen J.P., Perlstein E.O., Rubinsztein D., Sarkar S., Wood S.L.S. Regulating Autophagy. Patent. 2008.
Not in our library
411.
Manjithaya R., Mishra P., Santhi Natesan S., Bats S., Ammanathan V., Chavalmane A. Method for Modulating Autophagy and Applications Thereof. Patent. 2017.
Not in our library
412.
Li M., Song J., Zeng Y., Liu L. MTOR-Independent Activator of TFEB for Autophagy Enhancement and Uses Thereof. U.S. Patent. 2016.
Not in our library
413.
Zaupa C., Hortelano J., Silvestre N., Spindler A. Combination Product with Autophagy Modulator. Patent. 2016.
Not in our library
414.
Halfon P. Treatment of Hepatitis C Virus Related Diseases Using Hydroxychloroquine or a Combination of Hydroxychloroquine and an Anti-Viral Agent. U.S. Patent. 2015.
Not in our library
415.
Dent P., Zukiwski A., Proniuk S. Enhancing the Anti-Tumor, Anti-Viral, and Anti-Protozoan Effects of 2-amino-n-[4-[5-phenanthren-2-yl-3-(trifluoromethyl) pyrazol-1-yl] phenyl]acetamide (osu-03012) and Other Pharmaceutical Drugs. Patent. 2016.
Not in our library
416.
Levine B.C., Shoji-Kawata S., Lichtarge O., Wilkins A.D. Autophagy-inducing peptide. Patent. 2017.
Not in our library
417.
Liu L., Ward D., Leung E.L.H., Yao X.J., Wong V.K.W., Luo L.X. Combination Treatment of RAS-Positive Diseases with PDE-Delta Inhibitor and Direct Autophagy Inhibitor. U.S. Patent. 2018.
Not in our library
418.
Kimmelman A.C., Mancias J.D., Harper J.W. Compositions and Methods for Modulating ncoa4-Mediated Autophagic Targeting of Ferritin. International and National Patent Collections. Patent. 2015.
Not in our library
419.
Hidenao S., Jun U., Koichi W. MicroRNA that Regulate Autophagy. Patent. 2017.
Not in our library
420.
Nicolas G., Vaulont S., Kahn A. Use of Hepcidin as a Regulator of Iron Homeostasis. U.S. Patent. 2007.
Not in our library
421.
Ganz T., Nemeth E., Kautz L. Erythroferrone and Erfe Polypeptides and Methods of Regulating Iron Metabolism. Patent. 2014.
Not in our library
422.
Schneider S.A., Bhatia K.P. Syndromes of neurodegeneration with brain iron accumulation. Semin. Pediatr. Neurol. 2012;19:57-66.
Not in our library10.1016/j.spen.2012.03.005
423.
Haack T.B., Hogarth P., Kruer M.C., Gregory A., Wieland T., Schwarzmayr T., Graf E., Sanford L., Meyer E., Kara E., et al. Exome sequencing reveals de novo WDR45 mutations causing a phenotypically distinct, X-linked dominant form of NBIA. Am. J. Hum. Genet. 2012;91:1144-1149.
Not in our library10.1016/j.ajhg.2012.10.019
424.
Saitsu H., Nishimura T., Muramatsu K., Kodera H., Kumada S., Sugai K., Kasai-Yoshida E., Sawaura N., Hoshino A., Ryujin F., et al. De novo mutations in the autophagy gene WDR45 cause static encephalopathy of childhood with neurodegeneration in adulthood. Nat Genet. 2013;45:445-449.
Not in our library10.1038/ng.2562
425.
Schneider S., Zorzi G., Nardocci N. Pathophysiology and treatment of neurodegeneration with brain iron accumulation in the pediatric population. Curr. Treat Opt. Neurol. 2013;15:652-667.
Not in our library10.1007/s11940-013-0254-5
426.
Lu Q., Yang P., Huang X., Hu W., Guo B., Wu F. The WD40 repeat PtdIns(3)P-binding protein EPG-6 regulates progression of omegasomes to autophagosomes. Dev. Cell. 2011;21:343-357.
Not in our library10.1016/j.devcel.2011.06.024
427.
Polson H.E., de Lartigue J., Rigden D.J., Reedijk M., Urbé S., Clague M.J., Tooze S.A. Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phagophores and positively regulates LC3 lipidation. Autophagy. 2010;6:506-522.
Not in our library10.4161/auto.6.4.11863
428.
Baumgart D.C., Sandborn W.J. Crohn’s disease. Lancet. 2012;380:1590-1605.
Not in our library10.1016/s0140-6736(12)60026-9
429.
Saitoh T., Fujita N., Jang M.H., Uematsu S., Yang B.G., Satoh T. Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature. 2008;456:264-268.
Not in our library10.1038/nature07383
430.
Fujita N., Saitoh T., Kageyama S., Akira S., Noda T., Yoshimori T. Differential involvement of Atg16L1 in Crohn disease and canonical autophagy: Analysis of the organization of the Atg16L1 complex in fibroblasts. J. Biol. Chem. 2009;284:32602-32609.
Not in our library10.1074/jbc.m109.037671
431.
Stappenbeck T.S., Rioux J.D., Mizoguchi A., Saitoh T., Huett A., Darfeuille-Michaud A., Wileman T., Mizushima N., Carding S., et al. Crohn disease: A current perspective on genetics, autophagy and immunity. Autophagy. 2011;7:355-374.
Not in our library10.4161/auto.7.4.13074
432.
Oz-Levi D., Ben-Zeev B., Ruzzo E.K., Hitomi Y., Gelman A., Pelak K., Anikster Y., Reznik-Wolf H., Bar-Joseph I., Olender T., et al. Mutation in TECPR2 reveals a role for autophagy in hereditary spastic paraparesis. Am. J. Hum. Genet. 2012;91:1065-1072.
Not in our library10.1016/j.ajhg.2012.09.015
433.
Vantaggiato C., Crimella C., Airoldi G., Polishchuk R., Bonato S., Brighina E., Scarlato M., Musumeci O., Toscano A., Martinuzzi A., et al. Defective autophagy in spastizin mutated patients with hereditary spastic paraparesis type 15. Brain. 2013;136:3119-3139.
Not in our library10.1093/brain/awt227
434.
Vantaggiato C., Panzeri E., Castelli M., Citterio A., Arnoldi A., Santorelli F.M., Liguori R., Scarlato M., Musumeci O., Toscano A., et al. ZFYVE26/SPASTIZIN and SPG11/SPATACSIN mutations in hereditary spastic paraplegia types AR-SPG15 and AR-SPG11 have different effects on autophagy and endocytosis. Autophagy. 2019;15:34-57.
Not in our library10.1080/15548627.2018.1507438
435.
Rothaug M., Stroobants S., Schweizer M., Peters J., Zunke F., Allerding M., D’Hooge R., Saftig P., Blanz J. LAMP-2 deficiency leads to hippocampal dysfunction but normal clearance of neuronal substrates of chaperone-mediated autophagy in a mouse model for Danon disease. Acta Neuropathol. Commun. 2015;3:6.
Not in our library10.1186/s40478-014-0182-y
436.
Ng K.M., Mok P.Y., Butler A.W., Ho J.C., Choi S.W., Lee Y.K., Lai W.H., Au K.W., Lau Y.M., Wong L.Y., et al. Amelioration of X-linked related autophagy failure in Danon disease with DNA methylation inhibitor. Circulation. 2016;134:1373-1389.
Not in our library10.1161/circulationaha.115.019847
437.
Rowland T.J., Sweet M.E., Mestroni L., Taylor M.R. Danon disease—Dysregulation of autophagy in a multisystem disorder with cardiomyopathy. J. Cell Sci. 2016;129:2135-2143.
Not in our library10.1242/jcs.184770
438.
Mindell J.A. Lysosomal acidification mechanisms. Annu. Rev. Physiol. 2012;74:69-86.
Not in our library10.1146/annurev-physiol-012110-142317
439.
Dowling J.J., Moore S.A., Kalimo H., Minassian B.A. X-linked myopathy with excessive autophagy: A failure of self-eating. Acta Neuropathol. 2015;129:383-390.
Not in our library10.1007/s00401-015-1393-4
440.
Ruggieri A., Ramachandran N., Wang P., Haan E., Kneebone C., Manavis J., Morandi L., Moroni I., Blumbergs P., Mora M., et al. Non-coding VMA21 deletions cause X-linked myopathy with excessive autophagy. Neuromuscular Disord. 2015;25:207-211.
Not in our library10.1016/j.nmd.2014.11.014
441.
Zhao C.F., Herrington D.M. The function of cathepsins B, D, and X in atherosclerosis. Am. J. Cardiovasc. Dis. 2016;6:163-170.
Not in our library
442.
Nogalska A., D’Agostino C., Terracciano C., Engel W.K., Askanas V. Impaired autophagy in sporadic inclusion-body myositis and in endoplasmic reticulum stress-provoked cultured human muscle fibers. Am. J. Pathol. 2010;177:1377-1387.
Not in our library10.2353/ajpath.2010.100050
443.
Shu X., Chen F., Pen Q., Lu X., Tian X., Wang Y., Wang G. Potential role of autophagy in T-cell survival in polymyositis and dermatomyositis. Mol. Med. Rep. 2017;16:1180-1188.
Not in our library10.3892/mmr.2017.6693
444.
Mastaglia F.L. Sporadic inclusion body myositis, variability in prevalence and phenotype and influence of the MHC. Acta Myol. 2009;28:66-71.
Not in our library
445.
Ozawa T., Koide R., Nakata Y., Saitsu H., Matsumoto N., Takahashi K., Nakano I., Orimo S. A novel WDR45 mutation in a patient with static encephalopathy of childhood with neurodegeneration in adulthood (SENDA). Am. J. Med. Genet. A. 2014;164:2388-2390.
Not in our library10.1002/ajmg.a.36635
446.
D’souza R.S., Levandowski C., Slavov D., Graw S.L., Allen L.A., Adler E., Mestroni L., Taylor M.R. Danon disease: Clinical features, evaluation, and management. Circ. Heart Fail. 2014;7:843-849.
Not in our library10.1161/circheartfailure.114.001105
447.
Cullup T., Kho A.L., Dionisi-Vici C., Brandmeier B., Smith F., Urry Z., Simpson M.A., Yau S., Bertini E., McClelland V., et al. Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy. Nat Genet. 2013;45:83-87.
Not in our library10.1038/ng.2497
448.
Zhao Y.G., Zhao H., Sun H., Zhang H. Role of Epg5 in selective neurodegeneration and Vici syndrome. Autophagy. 2013;9:1258-1262.
Not in our library10.4161/auto.24856
449.
Sarkar S., Carroll B., Buganim Y., Maetzel D., Ng A.H., Cassady J.P., Cohen M.A., Chakraborty S., Wang H., Spooner E., et al. Impaired autophagy in the lipid-storage disorder Niemann-Pick type C1 disease. Cell Rep. 2013;5:1302-1315.
Not in our library10.1016/j.celrep.2013.10.042
450.
Todd A.G., McElroy J.A., Grange R.W., Fuller D.D., Walter G.A., Byrne B.J., Falk D.J. Correcting neuromuscular deficits with gene therapy in Pompe disease. Ann. Neurol. 2015;78:222-234.
Not in our library10.1002/ana.24433
451.
Sun K., Deng W., Zhang S., Cai N., Jiao S., Song J., Wei L. Paradoxical roles of autophagy in different stages of tumorigenesis, protector for normal or cancer cells. Cell Biosci. 2013;3:35.
Not in our library10.1186/2045-3701-3-35
452.
Watson A.S., Mortensen M., Simon A.K. Autophagy in the pathogenesis of myelodysplastic syndrome and acute myeloid leukemia. Cell Cycle. 2011;10:1719-1725.
Not in our library10.4161/cc.10.11.15673
453.
Exploring the Role of Autophagy-Related Gene 5 (ATG5) Yields Important Insights Into Autophagy in Autoimmune/Autoinflammatory Diseases · 2018
No notice
454.
Yao Q.M., Zhu Y.F., Wang W., Song Z.Y., Shao X.Q., Li L., Song R.H., An X.F., Qin Q., Li Q., et al. Polymorphisms in autophagy-related gene IRGM are associated with susceptibility to autoimmune thyroid diseases. Biomed. Res. Int. 2018;2018:7959707.
Not in our library10.1155/2018/7959707
455.
Polymorphisms in autophagy genes are associated with paget disease of bone. · 2015
Not checked
456.
Comincini S., Manai F., Meazza C., Pagani S., Martinelli C., Pasqua N., Pelizzo G., Biggiogera M., Bozzola M. Identification of autophagy-related genes and their regulatory mirnas associated with celiac disease in children. Int. J. Mol. Sci. 2017;18:391.
Not in our library10.3390/ijms18020391
457.
Barboza L.A., Ghisi N.C. Evaluating the current state of the art of Huntington disease research: A scientometric analysis. Braz. J. Med. Biol. Res. 2018;51:e6299.
Not in our library10.1590/1414-431x20176299
458.
Shirakabe A., Ikeda Y., Sciarretta S., Zablocki D.K., Sadoshima J. Aging and autophagy in the heart. Circ. Res. 2016;118:1563-1576.
Not in our library10.1161/circresaha.116.307474
459.
Sun T., Li M.Y., Li P.F., Cao J.M. MicroRNAs in cardiac autophagy: Small molecules and big role. Cells. 2018;7:104.
Not in our library10.3390/cells7080104
460.
Heckmann B.L., Yang X., Zhang X., Liu J. The autophagic inhibitor 3-methyladenine potently stimulates PKA-dependent lipolysis in adipocytes. Br. J. Pharmacol. 2013;168:163-171.
Not in our library10.1111/j.1476-5381.2012.02110.x
461.
Huang S., Sinicrope F.A. Celecoxib-induced apoptosis is enhanced by ABT-737 and by inhibition of autophagy in human colorectal cancer cells. Autophagy. 2010;6:256-269.
Not in our library10.4161/auto.6.2.11124
462.
Oot R.A., Couoh-Cardel S., Sharma S., Stam N.J., Wilkens S. Breaking up and making up: The secret life of the vacuolar H+-ATPase. Protein Sci. 2017;26:896-909.
Not in our library10.1002/pro.3147
463.
Wu Y.C., Wu W.K., Li Y., Yu L., Li Z.J., Wong C.C., Li H.T., Sung J.J., Cho C.H. Inhibition of macroautophagy by bafilomycin A1 lowers proliferation and induces apoptosis in colon cancer cells. Biochem. Biophys. Res. Commun. 2009;382:451-456.
Not in our library10.1016/j.bbrc.2009.03.051
464.
Yuan N., Song L., Zhang S., Lin W., Cao Y., Xu F., Fang Y., Wang Z., Zhang H., Li X., et al. Bafilomycin A1 targets both autophagy and apoptosis pathways in pediatric B-cell acute lymphoblastic leukemia. Haematologica. 2015;100:345-356.
Not in our library10.3324/haematol.2014.113324
465.
Kissing S., Rudnik S., Damme M., Lüllmann-Rauch R., Ichihara A., Kornak U., Eskelinen E.L., Jabs S., Heeren J., et al. Disruption of the vacuolar-type H+-ATPase complex in liver causes MTORC1-independent accumulation of autophagic vacuoles and lysosomes. Autophagy. 2017;13:670-685.
Not in our library10.1080/15548627.2017.1280216
466.
Yano K., Yanagisawa T., Mukae K., Niwa Y., Inoue Y., Moriyasu Y. Dissection of autophagy in tobacco BY-2 cells under sucrose starvation conditions using the vacuolar H(+)-ATPase inhibitor concanamycin A and the autophagy-related protein Atg8. Plant Signal Behav. 2015;10:e1082699.
Not in our library10.1080/15592324.2015.1082699
467.
Rez G., Kovacs J. Prevention by cycloheximide of cellular autophagy induced by hyperosmotic sucrose or cadmium chloride in mouse pancreatic acinar cells. Acta Biol. Acad. Sci. Hung. 1973;24:201-205.
Not in our library
468.
Zhu Z.C., Liu J.W., Li K., Zheng J., Xiong Z.Q. KPNB1 inhibition disrupts proteostasis and triggers unfolded protein response-mediated apoptosis in glioblastoma cells. Oncogene. 2018;37:2936-2952.
Not in our library10.1038/s41388-018-0180-9
469.
Machiya Y., Hara S., Arawaka S., Fukushima S., Sato H., Sakamoto M., Koyama S., Kato T. Phosphorylated alpha-synuclein at Ser-129 is targeted to the proteasome pathway in a ubiquitin-independent manner. J. Biol. Chem. 2010;285:40732-40744.
Not in our library10.1074/jbc.m110.141952
470.
Rainsford K.D., Parke A.L., Clifford-Rashotte M., Kean W.F. Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases. Inflammopharmacology. 2015;23:231-269.
Not in our library10.1007/s10787-015-0239-y
471.
Harhaji-Trajkovic L., Arsikin K., Kravic-Stevovic T., Petricevic S., Tovilovic G., Pantovic A., Zogovic N., Ristic B., Janjetovic K., Bumbasirevic V., et al. Chloroquine-mediated lysosomal dysfunction enhances the anticancer effect of nutrient deprivation. Pharm. Res. 2012;29:2249-2263.
Not in our library10.1007/s11095-012-0753-1
472.
McAfee Q., Zhang Z., Samanta A., Levi S.M., Ma X.H., Piao S., Lynch J.P., Uehara T., Sepulveda A.R., Davis L.E., et al. Autophagy inhibitor Lys05 has single-agent antitumor activity and reproduces the phenotype of a genetic autophagy deficiency. Proc. Natl. Acad. Sci. USA. 2012;109:8253-8258.
Not in our library10.1073/pnas.1118193109
473.
Moriyasu Y., Inoue Y. Use of protease inhibitors for detecting autophagy in plants. Methods Enzymol. 2008;451:557-580.
Not in our library10.1016/s0076-6879(08)03232-1
474.
Jung M., Lee J., Seo H.Y., Lim J.S., Kim E.K. Cathepsin inhibition-induced lysosomal dysfunction enhances pancreatic beta-cell apoptosis in high glucose. PLoS ONE. 2015;10:e0116972.
Not in our library10.1371/journal.pone.0116972
475.
Tanida I., Minematsu-Ikeguchi N., Ueno T., Kominami E. Lysosomal turnover, but not a cellular level, of endogenous LC3 is a marker for autophagy. Autophagy. 2005;1:84-91.
Not in our library10.4161/auto.1.2.1697
476.
Redmann M., Benavides G.A., Berryhill T.F., Wani W.Y., Ouyang X., Johnson M.S., Ravi S., Barnes S., Darley-Usmar V.M., Zhang J. Inhibition of autophagy with bafilomycin and chloroquine decreases mitochondrial quality and bioenergetic function in primary neurons. Redox Biol. 2017;11:73-81.
Not in our library10.1016/j.redox.2016.11.004
477.
Tanida I. Autophagy basics. Microbiol. Immunol. 2011;55:1-11.
Not in our library10.1111/j.1348-0421.2010.00271.x
478.
Chen Y., Liersch R., Detmar M. The miR-290-295 cluster suppresses autophagic cell death of melanoma cells. Sci. Rep. 2012;2:808.
Not in our library10.1038/srep00808
479.
Huang Y., Chuang A.Y., Ratovitski E.A. Phospho-ΔNp63α/miR-885-3p axis in tumor cell life and cell death upon cisplatin exposure. Cell Cycle. 2011;10:3938-3947.
Not in our library10.4161/cc.10.22.18107
480.
Menghini R., Casagrande V., Marino A., Marchetti V., Cardellini M., Stoehr R. MiR-216a: A link between endothelial dysfunction and autophagy. Cell Death Dis. 2014;5:e1029.
Not in our library10.1038/cddis.2013.556
481.
miR-17-5p Downregulation Contributes to Paclitaxel Resistance of Lung Cancer Cells through Altering Beclin1 Expression · 2014
No notice
482.
Jing Z., Han W., Sui X., Xie J., Pan H. Interaction of autophagy with microRNAs and their potential therapeutic implications in human cancers. Cancer Lett. 2015;356:332-338.
Not in our library10.1016/j.canlet.2014.09.039
483.
Lassen K.G., Xavier R.J. Genetic control of autophagy underlies pathogenesis of inflammatory bowel disease. Mucosal Immunol. 2017;10:589-597.
Not in our library10.1038/mi.2017.18
484.
The T300A Crohn’s disease risk polymorphism impairs function of the WD40 domain of ATG16L1 · 2016
Not checked
485.
Kim D.H., Sarbassov D.D., Ali S.M., King J.E., Latek R.R., Erdjument-Bromage H., Tempst P., Sabatini D.M. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell. 2002;110:163-175.
Not in our library10.1016/s0092-8674(02)00808-5
486.
Gentilella A., Kozma S.C., Thomas G. A liaison between mTOR signalling, ribosome biogenesis and cancer. Biochim. Biophys. Acta. 2015;1849:812-820.
Not in our library10.1016/j.bbagrm.2015.02.005
487.
Frederick C., Ando K., Leroy K., Héraud C., Suain V., Buée L., Brion J.P. Rapamycin ester analog CCI-779/Temsirolimus alleviates tau pathology and improves motor deficit in mutant tau transgenic mice. J. Alzheimers Dis. 2015;44:1145-1156.
Not in our library10.3233/jad-142097
488.
Vignot S., Faivre S., Aguirre D., Raymond E. mTOR-targeted therapy of cancer with rapamycin derivatives. Ann. Oncol. 2005;16:525-537.
Not in our library10.1093/annonc/mdi113
489.
Lin J.F., Lin Y.C., Yang S.C., Tsai T.F., Chen H.E., Chou K.Y., Hwang T.I. Autophagy inhibition enhances RAD001-induced cytotoxicity in human bladder cancer cells. Drug Des. Dev. Ther. 2016;10:1501-1513.
Not in our library10.2147/dddt.s95900
490.
Ma J., Yang S., Ma A., Pan X., Wang H., Li N., Liu S., Wu M. Expression of miRNA-155 in carotid atherosclerotic plaques of apolipoprotein E knockout (ApoE−/−) mice and the interventional effect of rapamycin. Int. Immunopharmacol. 2017;46:70-74.
Not in our library10.1016/j.intimp.2017.02.026
491.
Liu D., Liu Y., Chen G., He L., Tang C., Wang C., Yang D., Li H., Dong Z., Liu H. Rapamycin enhances repressed autophagy and attenuates aggressive progression in a rat model of IgA nephropathy. Am. J. Nephrol. 2017;45:293-300.
Not in our library10.1159/000456039
492.
Floto R.A., Sarkar S., Perlstein E.O., Kampmann B., Schreiber S.L., Rubinsztein D. Small molecule enhancers of rapamycin-induced TOR inhibition promote autophagy, reduce toxicity in Huntington’s disease models and enhance killing of mycobacteria by macrophages. Autophagy. 2007;3:620-622.
Not in our library10.4161/auto.4898
493.
Seidel K., Siswanto S., Fredrich M., Bouzrou M., Brunt E.R., van Leeuwen F.W., Kampinga H.H., Korf H.W., et al. Polyglutamine aggregation in Huntington’s disease and spinocerebellar ataxia type 3: Similar mechanisms in aggregate formation. Neuropathol. Appl. Neurobiol. 2016;42:153-166.
Not in our library10.1111/nan.12253
494.
Mardones P., Rubinsztein D.C., Hetz C. Mystery solved: Trehalose kick starts autophagy by blocking glucose transport. Sci. Signal. 2016;9:fs2.
Not in our library10.1126/scisignal.aaf1937
495.
Meier J.L., Grose C. Focus: Drug development: Variable effects of autophagy induction by trehalose on Herpes viruses depending on conditions of infection. Yale J. Biol. Med. 2017;90:25.
Not in our library
496.
Honma Y., Sato-Morita M., Katsuki Y., Mihara H., Baba R., Harada M. Trehalose activates autophagy and decreases proteasome inhibitor-induced endoplasmic reticulum stress and oxidative stress-mediated cytotoxicity in hepatocytes. Hepatol. Res. 2018;48:94-105.
Not in our library10.1111/hepr.12892
497.
Chen X., Li M., Li L., Xu S., Huang D., Ju M., Huang J., Chen K., Gu H. Trehalose, sucrose and raffinose are novel activators of autophagy in human keratinocytes through an mTOR-independent pathway. Sci. Rep. 2016;6:28423.
Not in our library10.1038/srep28423
498.
He Q., Koprich J.B., Wang Y., Yu W.B., Xiao B.G., Brotchie J.M., Wan J. Treatment with trehalose prevents behavioral and neurochemical deficits produced in an AAV α-Synuclein rat model of Parkinson’s disease. Mol. Neurobiol. 2016;53:2258-2268.
Not in our library10.1007/s12035-015-9173-7
499.
Kruger U., Wang Y., Kumar S., Mandelkow E.M. Autophagic degradation of tau in primary neurons and its enhancement by trehalose. Neurobiol. Aging. 2012;33:2291-2305.
Not in our library10.1016/j.neurobiolaging.2011.11.009
500.
Aguib Y., Heiseke A., Gilch S., Riemer C., Baier M., Schatzl H.M., Ertmer A. Autophagy induction by trehalose counteracts cellular prion infection. Autophagy. 2009;5:361-369.
Not in our library10.4161/auto.5.3.7662
501.
Wada S., Kubota Y., Sawa R., Umekita M., Hatano M., Ohba S.I., Hayashi C., Igarashi M., Nomoto A. Novel autophagy inducers lentztrehaloses A., B and C. J. Antibiot. 2015;68:521-529.
Not in our library10.1038/ja.2015.23
502.
Motoi Y., Shimada K., Ishiguro K., Hattori N. Lithium and autophagy. ACS Chem. Neurosci. 2014;5:434-442.
Not in our library10.1021/cn500056q
503.
Kim Y.H., Rane S., Lussiernbb S., Andersen J.K. Lithium protects against oxidative stress-mediated cell death in alpha-synuclein over-expressing in vitro and in vivo models of Parkinson’s disease. J. Neurosci. Res. 2011;89:1666-1675.
Not in our library10.1002/jnr.22700
504.
Sarkar S., Floto R.A., Berger Z., Imarisio S., Cordenier A., Pasco M., Cook L.J., Rubinsztein D.C. Lithium induces autophagy by inhibiting inositol monophosphatase. J. Cell Biol. 2005;170:1101-1111.
Not in our library10.1083/jcb.200504035
505.
Xia Q., Zheng Y., Jiang W., Huang Z., Wang M., Rodriguez R., Jin X. Valproic acid induces autophagy by suppressing the Akt/mTOR pathway in human prostate cancer cells. Oncol. Lett. 2016;12:1826-1832.
Not in our library10.3892/ol.2016.4880
506.
Ji M.M., Wang L., Zhan Q., Xue W., Zhao Y., Zhao X., Xu P.P., Shen Y., Liu H., Janin A., et al. Induction of autophagy by valproic acid enhanced lymphoma cell chemosensitivity through HDAC-independent and IP3-mediated PRKAA activation. Autophagy. 2015;11:2160-2171.
Not in our library10.1080/15548627.2015.1082024
507.
Pietrocola F., Lachkar S., Enot D.P., Niso-Santano M., Bravo-San Pedro J.M., Sica V., Izzo V., Maiuri M.C., Madeo F., Mariño G., et al. Spermidine induces autophagy by inhibiting the acetyltransferase EP300. Cell Death Differ. 2015;22:509-516.
Not in our library10.1038/cdd.2014.215
508.
Lee I.H., Finkel T. Regulation of autophagy by the p300 acetyltransferase. J. Biol. Chem. 2009;284:6322-6328.
Not in our library10.1074/jbc.m807135200
509.
Pietrocola F., Malik S.A., Mariño G., Vacchelli E., Senovilla L., Chaba K., Niso-Santano M., Maiuri M.C., Madeo F., Kroemer G. Coffee induces autophagy in vivo. Cell Cycle. 2014;13:1987-1994.
Not in our library10.4161/cc.28929
510.
Madeo F., Zimmermann A., Maiuri M.C., Kroemer G. Essential role for autophagy in life span extension. J. Clin. Investig. 2015;125:85-93.
Not in our library10.1172/jci73946
511.
Identification of Host-Targeted Small Molecules That Restrict Intracellular Mycobacterium tuberculosis Growth · 2014
No notice
512.
Functional drug screening reveals anticonvulsants as enhancers of mTOR‐independent autophagic killing of Mycobacterium tuberculosis through inositol depletion · 2014
No notice
513.
Sarkar S., Ravikumar B., Floto R.A., Rubinsztein D.C. Rapamycin and mTOR-independent autophagy inducers ameliorate toxicity of polyglutamine-expanded huntingtin and related proteinopathies. Cell Death Differ. 2009;16:46-56.
Not in our library10.1038/cdd.2008.110
514.
Renna M., Jimenez-Sanchez M., Sarkar S., Rubinsztein D.C. Chemical inducers of autophagy that enhance the clearance of mutant proteins in neurodegenerative diseases. J. Biol. Chem. 2010;285:11061-11067.
Not in our library10.1074/jbc.r109.072181
515.
Tsai H.H., Lai H.Y., Chen Y.C., Li C.F., Huang H.S., Liu H.S., Tsai Y.S., Wang J.M. Metformin promotes apoptosis in hepatocellular carcinoma through the CEBPD-induced autophagy pathway. Oncotarget. 2017;8:13832-13845.
Not in our library10.18632/oncotarget.14640
516.
Zhang H., Song Y., Li L., Zhang S.Y., Wu Q., Mei W.J., Liu H.M., Wang X.C. Phenanthroimidazole derivatives act as potentinducer of autophagy by activating DNA damage pathway. Bioorg. Chem. 2019;19:102940.
Not in our library10.1016/j.bioorg.2019.102940
517.
Zhang S.H., Wu H.M., Li S., Wang M.Z., Fang L., Liu R.Y. Melatonin enhances autophagy and decreases apoptosis induced by nanosilica in RAW264.7 cells. IUBMB Life. 2019.
Not in our library10.1002/iub.2055
518.
Liang Q.P., Xu T.Q., Liu B.L., Lei X.P., Hambrook J.R., Zhang D.M., Zhou G.X. Sasanquasaponin ΙΙΙ from Schima crenata Korth induces autophagy through Akt/mTOR/p70S6K pathway and promotes apoptosis in human melanoma A375 cells. Phytomedicine. 2018;20:152769.
Not in our library10.1016/j.phymed.2018.11.029
519.
Wang L., Sun X., Zhu M., Du J., Xu J., Qin X., Xu X., Song E. Epigallocatechin-3-gallate stimulate autophagy and reduces apoptosis levels in retinal Müller cells under high-glucose conditions. Exp. Cell Res. 2019;380:149-158.
Not in our library10.1016/j.yexcr.2019.04.014

Cited by papers we hold 7

Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies · 2023
No notice
Case Report: Danon Disease: Six Family Members and Literature Review · 2022
Not checked
Multidrug Resistance in Cancer: Understanding Molecular Mechanisms, Immunoprevention and Therapeutic Approaches · 2022
No notice
Role of glioblastoma stem cells in cancer therapeutic resistance: a perspective on antineoplastic agents from natural sources and chemical derivatives · 2021
No notice
Major advances in targeted protein degradation: PROTACs, LYTACs, and MADTACs · 2021
No notice
Roles of Autophagy in Oxidative Stress · 2020
No notice
Hypoxia and HIF Signaling: One Axis with Divergent Effects · 2020
No notice

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.