No retraction, correction or concern found when last checked on Oct 18, 2026.

Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury

Wiramon Rungratanawanich, Ying Qu, Xin Wang and 2 more

Experimental & Molecular Medicine · 2021 · Review · CC BY

Abstract

Advanced glycation end products (AGEs) are potentially harmful and heterogeneous molecules derived from nonenzymatic glycation. The pathological implications of AGEs are ascribed to their ability to promote oxidative stress, inflammation, and apoptosis. Recent studies in basic and translational research have revealed the contributing roles of AGEs in the development and progression of various aging-related pathological conditions, such as diabetes, cardiovascular complications, gut microbiome-associated illnesses, liver or neurodegenerative diseases, and cancer. Excessive chronic and/or acute binge consumption of alcohol (ethanol), a widely consumed addictive substance, is known to cause more than 200 diseases, including alcohol use disorder (addiction), alcoholic liver disease, and brain damage. However, despite the considerable amount of research in this area, the underlying molecular mechanisms by which alcohol abuse causes cellular toxicity and organ damage remain to be further characterized. In this review, we first briefly describe the properties of AGEs: their formation, accumulation, and receptor interactions. We then focus on the causative functions of AGEs that impact various aging-related diseases. We also highlight the biological connection of AGE–alcohol–adduct formations to alcohol-mediated tissue injury. Finally, we describe the potential translational research opportunities for treatment of various AGE- and/or alcohol-related adduct-associated disorders according to the mechanistic insights presented.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 18, 2026. Paragraph numbers are ours, so an answer can point at one.

Introduction

1Advanced glycation end products (AGEs) are potentially harmful heterogeneous molecules of irreversible products derived from nonenzymatic glycation. Reactions involving nonenzymatic glycation occur between the reactive carbonyl group of a reducing sugar and nucleic acids, lipids, or proteins. AGEs can be formed endogenously or provided by exogenous sources under normal and pathological conditions,. The pathological implications of AGEs are ascribed to their ability to produce reactive oxygen (ROS) and nitrogen (RNS) species, as well as oxidative stress and inflammation, leading to structural and functional protein alterations, cellular dysfunction and apoptosis, and ultimately multitissue/organ injuries. Cross-links formed by the interactions of AGEs with their cell surface receptors for advanced glycation end products (RAGEs) have been found during the development and progression of various aging-related diseases, such as diabetes, cardiovascular complications, kidney malfunctions, osteoporosis, cancer, neurodegenerative diseases, and liver disorders,

2Alcohol (ethanol), one of the most addictive substances consumed by billions of people, has been found to cause more than 200 diseases and injuries worldwide,. In the United States alone, more than 250 billion dollars are lost annually due to alcoholism-related disorders and their consequences. In addition, multiple millions of global deaths have been reported from excessive alcohol consumption due to acute and long-term consequences such as accidents, injuries, and a wide range of diseases,. Chronic misuse of alcohol promotes damage to multiple tissues and organs. It can lead to the development of various pathological states, such as alcohol use disorder, alcoholic liver disease, and alcohol-related brain damage, as well as increase the risk of cancer in the gastrointestinal tract, respiratory tract, breast, and liver,. However, despite the considerable amount of research in this area, the underlying molecular mechanisms by which alcohol exerts its cellular toxicity and organ damage remain to be further characterized.

3In this review, we first briefly describe the properties of AGEs: their formation, accumulation, and RAGE interactions. We then focus on the causative functions of AGEs that impact various aging-related diseases. In addition, we highlight the biological connections of AGE–alcohol–adduct formations in alcohol-mediated multiorgan damage. Finally, we briefly describe the potential translational research opportunities for treating various AGE- and/or alcohol-related adduct-associated disorders based on the mechanistic insights presented.

Endogenous AGEs

4Endogenous AGEs represent adducts that are produced and slowly accumulated within the body during the normal aging process and under the oxidative stress, inflammatory, and hyperglycemic (high blood sugar) conditions often observed in diabetes and other metabolic syndromes,,,. AGEs are formed by a nonenzymatic glycation reaction, also known as the Maillard reaction, between the carbonyl group of a reducing sugar and a free amino group (N-terminus, lysine, or arginine residue) of proteins or (adenine or guanine) of nucleic acids. This reaction is followed by a highly reversible nucleophilic addition reaction to generate a reversible Schiff base adduct, which is rearranged to a more stable and covalently bound Amadori product (e.g., hemoglobin A1c). Then, the Amadori product undergoes rearrangement, dehydration, and oxidation reactions to form irreversible products, AGEs, in the body. In addition to nonenzymatic glycation, AGEs can be formed through the polyol pathway and lipid peroxidation in the presence and absence of hyperglycemia, depending on the substrate type, reactant concentration, exposure time, and host cellular context–.

5Various factors are involved in promoting AGE formation. These factors include excessive and/or prolonged alcohol consumption, cigarette smoking, the intake of high fat/caloric diets and/or extensively processed food, renal status, homeostatic imbalance, inflammation, hyperglycemia, and oxidative stress–. For example, persistently high blood glucose, often observed in people with type 2 diabetes, increases the reservoir of substrate for accelerating AGE formation and activates protein kinase C and NADPH oxidases, producing ROS,. Additionally, elevated oxidative stress can act as a catalyst to stimulate AGE accumulation, while activation of AGEs can increase oxidative stress, creating a synergistic feed-forward loop to accelerate pathophysiological conditions–.

Exogenous AGEs

6Exogenous AGEs include dietary AGEs (e.g., foods and beverages such as soft drinks containing high fructose corn sirup and/or sugar) and cigarette smoke. Additionally, dietary AGEs can be produced during food preparation. This formation of dietary AGEs depends on various factors, such as (1) temperature. e.g., the food browning process; (2) water content. e.g., dry-heat cooking; (3) pH status, e.g., food processing at high pH; and (4) cooking time and method, e.g., long-term cooking or storage and frying or broiling. These variations activate the nonenzymatic Maillard reaction, leading to the formation of glycation products and AGEs,. For example, high heat and prolonged cooking time enhance the rate and amount of AGE production in diets. Foods with high pH values (up to 10) have elevated AGEs due to free amino groups under alkaline conditions. Putative examples of dietary AGEs are modern Western diets such as bakery goods, breakfast cereals, cheese, and meat cooked by a dry-heat method. In addition to dietary AGEs, cigarette smoke is found to contain reactive glycation products, which can increase AGE accumulation in the tissues and circulating blood of smokers.

7The amounts of AGEs in exogenous sources are usually much higher than those of endogenously produced AGEs–,. Thus, it is likely that the intake of foods and/or beverages with high levels of exogenous AGEs create more health problems than endogenously produced AGEs, although both exogenous and endogenous AGEs are similar in their biological functions and potentially act synergistically to stimulate oxidative stress, inflammation, and cellular damage, contributing to detrimental pathophysiology–,.

Intracellular AGEs

8AGEs gradually accumulate during the aging process through normal metabolic and glycation activities. The aggregation of AGEs from endogenous and/or exogenous sources can negatively affect the functions of many cells in the entire body, resulting in diverse cellular responses and ultimately cellular damage and degeneration. Intracellular AGE accumulation can stimulate aberrant protein glycation, abnormal protein folding, and the aggregation of irregular or oligomeric proteins, as well as elevated oxidative stress and inflammation and upregulated apoptotic signaling pathways. These changes can contribute to protein inactivation, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, cell apoptosis, and organ damage,. For instance, in neuronal tissues, the accumulation of AGEs induces glycation of α-synuclein and tau proteins, leading to protein dysfunction accompanied by the aggregation of harmful protein oligomers capable of initiating and developing neurodegenerative diseases,.

Extracellular AGEs

9AGEs are long-lived irreversibly formed molecules found in the circulatory system and tissues, particularly those with long-lasting proteins such as lens crystallins, cartilage, glomerular basement membrane, and extracellular matrix,. Cross-linking AGEs with extracellular matrix proteins, including laminin, elastin, and collagen, can alter the elasticity and function of tissues. In fact, higher levels of AGE cross-links are commonly detected in experimental animal models and autopsied tissue samples from people who are aging or have cancer, obesity, or diabetic complications–. In addition to long-lived proteins, AGEs can bind to proteins with short half-lives such as serum albumin, thereby activating RAGEs and inducing inflammatory responses followed by protein dysfunction and cell damage.

RAGEs and other AGE receptors

10A RAGE is a multiligand cell surface receptor in the immunoglobulin superfamily. Generally, RAGEs are expressed widely in various cells, such as endothelial cells, macrophages/monocytes, neutrophils, lymphocytes, microglia, astrocytes, and neurons, and organs, such as the brain, heart, lung, kidney, and liver,. However, under pathological conditions, RAGEs can be upregulated and participate in various aging-related pathophysiologies, such as adult-onset type 2 diabetes mellitus (DM), cardiovascular disorders, myocardial infarction, chronic kidney failure, pancreatitis, cancer, Alzheimer’s disease (AD), Parkinson’s disease (PD), hepatic fibrosis, and alcohol-mediated tissue injury,.

11The interaction of AGE-RAGE triggers intracellular and extracellular signaling pathways through the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), mitogen-activated protein kinases (MAPK), phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), NADPH oxidase, and nuclear factor-κB (NF-κB). Activation of these proteins usually increases oxidative stress and inflammation that, in turn, promotes RAGE expression in a positive feed-forward loop, contributing to chronic disease development–. In addition to an AGE, a RAGE binds diverse ligands, such as members of the S100 protein family, amyloid-β peptides (Aβ), prions, and high-mobility group protein B1 (HMGB1), which alter cellular functions and contribute to various pathophysiologies–.

12In addition to RAGEs, AGEs can interact with other cell surface receptors that possess the opposite function of RAGEs. These AGE cell surface receptors include AGE-R1, AGE-R2, AGE-R3, and scavenger receptors such as macrophage scavenger receptors, scavenger receptor class B type I and II (SR-BI, SR-BII), and cluster of differentiation 36 (CD36). The interaction of AGEs with these receptors can enhance their catabolism and clearance by modulating endocytosis and degradation,, suggesting a potentially adaptive defensive mechanism in the body to reduce the detrimental effects of increased glycation products.

AGEs and diabetes

13Chronic hyperglycemia, frequently observed in experimental models and human diabetes, exhibits elevated AGE formation, serum AGE levels, RAGE expression, and AGE-RAGE interactions. Consequently, these changes lead to increased oxidative stress, insulin resistance, inflammation, pancreatic β-cell dysfunction with apoptosis, and eventually diabetic complications, including retinopathy, neuropathy, cardiomyopathy, microvascular complications, and nephropathy–.

14Dietary AGEs have been found to disrupt and downregulate sirtuin1 (SIRT1) expression, resulting in the acetylation and inactivation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC1α), a master regulator of mitochondrial metabolism. AGEs also stimulate mitochondrial ROS production and c-Jun N-terminal protein kinase (JNK) and NADPH oxidase activity to induce mitochondrial dysfunction and oxidative stress–. Furthermore, increased oxidative stress and JNK/MAPK expression can contribute to pancreatic β-cell dysfunction with apoptosis, glucose-induced insulin secretion impairment, and subsequent insulin resistance, which is a key hallmark of type 2 DM. Restriction of dietary AGEs can reduce and/or reverse these effects by enhancing insulin sensitivity and upregulating AGE-R1 and SIRT1 expression while suppressing NF-κB, tumor necrosis factor-alpha (TNF-α), leptin, and serum AGEs in type 2 DM.

15AGEs play important roles in diabetic microvascular complications by cross-linking with extracellular matrix proteins, thereby altering vascular elasticity, structure, and function. In addition, the AGE-RAGE interaction further instigates pericyte apoptosis, vascular inflammation and permeability, and blood-tissue barrier breakdown. In contrast, the inhibition of RAGE by RAGE antiserum can prevent the toxicity induced by AGEs in diabetic microvascular complications.

AGEs and cardiovascular diseases

16AGEs can stimulate cardiovascular complications in the presence or absence of hyperglycemia. The accumulation and exposure to AGEs exacerbate oxidative stress and inflammation and initiate the oxidation of low-density lipoproteins (LDLs), which are harmful to cardiovascular function. In blood vessels, accumulated AGEs also interact with mononuclear, endothelial, and smooth muscle cells, resulting in cellular dysfunction, tissue damage, and atherosclerosis development–,. In acute myocardial infarction, increased expression of RAGE and its interaction with AGEs, HMGB1, and S100 induce cardiomyocyte apoptosis by activating the MAPK pathway,. Additionally, higher levels of circulating AGEs are positively correlated with the incidence of cardiovascular disorders and severity of coronary atherosclerosis and coronary artery disease independent of diabetic status–, suggesting a causal role of AGEs in cardiovascular diseases.

AGEs and kidney diseases

17The kidney is a highly specialized organ that reabsorbs many essential molecules, including water and salt, while removing potentially toxic compounds to protect the body. The accumulation of AGEs in the kidney can elevate oxidative stress and inflammation, contributing to renal failure. In humans, serum contains AGE peptides and free AGE adducts. AGE peptides are generally filtered by renal glomeruli and further reabsorbed by proximal convoluted tubules and eliminated from the body in the form of free AGE adducts in the urine,. Increased circulating AGEs can accumulate in the renal glomeruli and enhance collagen and laminin production in the extracellular matrix together with proximal tubular senescence, oxidative stress, and inflammatory processes. On the other hand, acute/chronic kidney disease and end-stage renal failure can reduce AGE clearance. Consequently, glomerular and tubular cells are exposed to potentially harmful AGEs for extended periods of time owing to the lower rates of glomerular filtration. These changes lead to accelerated progression and/or exacerbation of kidney malfunction and nephropathy along with greater amounts of AGEs in the circulation,.

18In addition, AGEs can be produced in renal mesangial cells and induce the expression of monocyte chemoattractant protein-1 (MCP-1). AGEs also activate NF-κB, MAPK, and protein kinase C (PKC) to promote mesangial proliferative inhibition, hypertrophy, and apoptosis,. Similarly, the AGE-RAGE interaction in the kidney can increase oxidative stress, inflammation, and fibrosis by stimulating connective tissue growth factor (CTGF), transforming growth factor-β (TGF-β), MAPK, NF-κB and PKC pathways to develop podocyte damage, glomerular hypertrophy, proteinuria, and ultimately end-stage renal failure,,. The RAGE ligand HMGB1 also plays a causal role in renal inflammation by enhancing ERK1/2, TNF-α, interleukin (IL)-6, and MCP-1, leading to nephropathy and chronic kidney disease,.

AGEs and obesity

19Dietary and endogenous AGEs and the AGE-RAGE interaction can promote oxidative stress and inflammation, contributing to the accelerated progression of obesity-related complications such as elevated serum AGEs, insulin resistance, AGE accumulation, and elevated proinflammatory cytokines in adipose tissues,, although consumption of dietary AGEs does not necessarily increase obesity based on its marginal association with increased body weight gain,. Adipose tissues also produce molecular RAGE ligands (such as HMGB-1) and RAGE-inducible molecules (e.g., MCP-1 and IL-6). Upon RAGE interaction, these bound molecules activate their own production in adipose tissues, suggesting a causal role of RAGE signaling in the inflammatory pathway,. In addition to dietary AGEs, endogenous AGEs can be trapped and accumulated in adipose tissues, and AGE accumulation can be prevented by RAGE inhibition.

20AGEs are reported to modify energy balance by disrupting hypothalamic function. Aggregated AGEs can activate the JNK, Iκ-B kinase (IKK), NF-κB, and TNF-α pathways to trigger hypothalamic insulin and leptin resistance, resulting in hypothalamic dysfunction, imbalanced energy control, and subsequently elevated food consumption and body weight with obesity and metabolic syndromes.

AGEs and osteoporosis

21Body bone mass is determined by the delicate balance between osteoclasts and osteoblasts involved in regulating bone formation, differentiation, and apoptosis in response to various stimuli. In bone, accumulated AGEs can increase osteoclast generation while decreasing osteoblast growth and differentiation. Initially, AGEs enhance the levels of osterix, a transcription factor that promotes osteoblast differentiation and bone formation. However, chronic AGE accumulation induces osteoblast apoptosis through activation of proapoptotic caspase-3, MAPK, and intracellular ROS generation–, indicating an intricate role for AGEs in bone physiology and remodeling.

22The interaction of AGE-RAGE augments the production of proinflammatory cytokines and suppresses osteoblast differentiation via the Wnt, PI3K, and ERK1/2 signaling pathways. Moreover, RAGE binding to its ligands (such as HMGB1 and S100) also triggers the production or activation of TNF-α, IL-1β, caspase-3, MAPK, NF-κB, vascular endothelial growth factor (VEGF), and matrix metalloproteinase 13 (MMP-13), negatively affecting the mass and structural composition of bone. Notably, several conditions, including aging, diabetes, renal failure, tobacco smoking, and excessive alcohol consumption that induce AGE accumulation and AGE-RAGE interaction, are risk factors for increased bone fracture and osteoporosis,.

AGEs and cancer

23Elevated amounts of AGEs are observed in tumor tissues in cancer. Increased AGEs and AGE-RAGE interactions provide a link to cancer initiation, progression, migration, and metastasis,. The binding of AGEs to RAGE triggers extracellular matrix glycation, NADPH oxidase activity, local hypoxia, VEGF expression, and NF-κB activation to produce oxidative stress and inflammation, supporting the cancer microenvironment and promoting tumoral angiogenesis and proliferation,.

24The overexpression of RAGE and its interaction with a ligand are associated with various types of cancer. RAGE is highly upregulated in metastatic and aggressive breast, ovarian, and pancreatic cancer, acting as a promotor of the progression of premalignant precursors to invasive carcinoma,. In hepatocellular carcinoma (HCC), RAGE overexpression and interaction with HMGB1 induce tumor-associated macrophage activation and NF-κB expression to promote tumoral proliferation, invasion, and metastasis,. After binding with S100, RAGE also contributes to the epithelial-mesenchymal cell transition and cell migration, which is associated with tumor invasion and metastasis in cervical cancer and osteosarcomas, suggesting a contributing role for RAGE in tumor malignancy. Furthermore, in cigarette smokers, elevated levels of RAGE are positively correlated with the development of oral squamous cell, lung, and breast carcinoma,.

AGEs and gut microbiome-associated diseases

25The gut microbiota plays a critical role in regulating body function by producing diverse metabolites and influencing the gut-liver-brain axis and other pathways, such as immune system pathways. The composition and function of gut flora can be affected by endogenous and exogenous factors, particularly food consumption with different levels of dietary AGEs,.

26In the body, less than 30% of dietary AGEs are absorbed in the intestine after ingestion, and less than 15% are excreted in urine and feces, leading to a hypothesis that the remaining unabsorbed AGEs are degraded by gut microorganisms. The intestinal microbiota produces deglycating enzymes to digest AGEs, which are utilized for energy production. As a result of this mechanism, unabsorbed AGEs may play a role in modulating the composition and number of intestinal microflora.

27AGEs can modify gut microbiota composition by triggering the growth of particular microbiomes, resulting in the loss of microbial diversity and an increased possibility of intestinal leakiness,. Elevated accumulation of AGEs can enhance gut barrier dysfunction, intestinal permeability, and bacterial translocation by stimulating the production and release of proinflammatory cytokines, potentially toxic metabolites and bacterial products, as well as causing intestinal epithelial cell damage, contributing to systemic endotoxemia, inflammation, and multiorgan injury. AGE-modulated gut microflora is also associated with the pathogenesis of type 2 DM, obesity, neurodegenerative diseases such as AD, and end-stage renal failure, where restriction of dietary AGEs can improve the gut microbial composition and subsequently attenuate disease conditions,.

AGEs and neurodegenerative diseases

28The brain is a highly specialized organ with tightly regulated motor, behavior, neurocognitive, and executive functions. However, it generally lacks defensive or protective enzymes/proteins compared to peripheral tissues such as the liver and kidney. Thus, under normal conditions, the brain is protected by a special functional system, the blood-brain barrier (BBB). In the brain, AGEs can be produced as a result of elevated oxidative stress during aging or chronic exposure to toxic agents such as alcohol (ethanol), n-6 fatty acid-containing high-fat Western diets, and sugary soft drinks. Oxidative stress can also be generated due to AGE formation in the brain. This feed-forward process creates a vicious cycle that exacerbates oxidative damage with the subsequent initiation and progression of neurodegenerative diseases,. However, the amounts of plasma AGEs, which can stimulate the aggregation of specifically modified proteins, are different in Alzheimer’s and Parkinson’s disease patients in a sex-dependent manner, thus requiring a careful interpretation of test results. Similar to AGEs, RAGEs are significantly or markedly expressed in many areas of the brain, such as the cortex, hippocampus, cerebellum, and substantia nigra– during the development of neurodegenerative diseases. Activated microglial cells produce and secrete AGE-albumin to induce RAGE expression in neurons and promote neuronal cell death, thereby contributing to neurodegenerative disorders,. Additionally, the accumulation of AGEs and the AGE-RAGE interaction greatly induce reactive gliosis and the NF-κB proinflammatory pathway, leading to cellular stress, activated gliosis, and eventually neuronal degeneration.

AGEs and Alzheimer’s disease

29Various forms of AGEs are markedly aggregated in neuronal plaques in the brain as well as in the serum and cerebrospinal fluid (CSF) in experimental models and autopsied brains from AD patients compared with the corresponding controls. Accumulated AGEs can accelerate the formation of Aβ, tau, and amyloid precursor protein (APP) and induce the hyperphosphorylation of tau and the cross-linking of AGE-Aβ, leading to an increase in these aggregates. AGEs also suppress SIRT1 expression and stimulate inducible nitric oxide synthase (iNOS) and caspase-3 to enhance neuronal apoptosis and/or degeneration with elevated gliosis.

30One of the most abundant AGE-protein adducts in the brain is the AGE-albumin adduct, which was confirmed by mass spectral analysis, and causes RAGE overexpression in primary neurons in human AD brains. The formation of the AGE-albumin adduct is intensified by elevated oxidative stress and Aβ aggregation. Aβ is also produced by the AGE-albumin-RAGE interaction, which in turn supports AGE-albumin adduct formation in a positive feed-forward cycle. The binding of the AGE-albumin adduct to RAGE provides a link to neuronal apoptosis by activating the proapoptotic JNK and Bcl-2-associated X protein (Bax) pathways. In addition to AGEs and AGE adducts, HMGB1 and Aβ can bind RAGEs to activate the NF-κB, ERK1/2, p38, JNK, PI3K, Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways, leading to neuronal cell death and neurodegeneration. Furthermore, AGEs cross-linked with Aβ can also decrease the ability of microglia to clear plaques.

AGEs and Parkinson’s disease

31Dietary AGEs promote AGE formation in the substantia nigra. In PD brains, AGEs can accumulate early in newly formed Lewy bodies, suggesting that AGEs could play a contributing role in Lewy body formation in developing PD. AGEs cross-linked with α-synuclein are also present in PD brains, resulting in the aggregation of α-synuclein toxic oligomers,. Moreover, RAGE can interact with S100 in PD brains, activating the NF-κB and TNF-α signaling pathways to promote dopaminergic neuronal death and subsequent neurodegeneration in PD,. AGE-albumin, the most abundant AGE product in the human PD brain, is synthesized by activated microglial cells. Aggregated AGE-albumin upregulates RAGE, leading to the apoptosis of primary dopamine neurons in the brain.

AGEs and liver diseases

32The liver plays a vital role in the metabolism and synthesis of various essential molecules and proteins needed for many other organs. It is involved in the catabolism and elimination of circulating AGEs using liver sinusoidal endothelial cells and Kupffer cells. This function of the liver declines during the aging process and in various liver diseases, resulting in the accumulation of AGEs or their aggregates,.

33Intracellular AGE accumulation is observed in animal models of hepatic steatosis and other advanced liver diseases, such as hepatic inflammation (steatohepatitis) and fibrosis/cirrhosis. Accumulated AGEs in hepatocytes can stimulate apoptosis and inflammation, leading to cellular dysfunction, steatosis, and ultimately nonalcoholic fatty liver disease (NAFLD)–.

34Endogenous and exogenous AGEs provoke the initiation and progression of NAFLD. However, consumption of dietary AGEs from sources such as fructose- or sucrose-enriched diets and/or soft drinks can worsen liver fibrosis faster than consumption of endogenous AGEs. The aggregation of AGEs decreases the levels of the most important cellular antioxidant peptides, glutathione (GSH), SIRT1, and tissue inhibitor of metalloproteinase 3 (TIMP3), accompanied by increased oxidative stress and inflammation, promoting inflammatory liver injury and fibrosis in experimental animal models and NAFLD patients–,–.

35Accumulated AGEs and AGE-RAGE interactions in these cells augment the generation of ROS and the activation of MAPK and NF-κB pathways, leading to inflammatory cell death in the parenchyma and tissue remodeling processes during fibrosis,.

36Increased amounts of RAGE are also observed in the liver of hepatocellular carcinoma (HCC), and its level is significantly greater than it is liver affected by hepatitis and healthy liver specimens. The amounts of serum AGEs are also higher in HCC than in NASH and healthy liver specimens. In HCC, the AGE-RAGE interaction is associated with angiogenesis and tumor proliferation and invasion, which are ameliorated by RAGE inhibition. These results suggest an important role for AGEs and RAGE in promoting NAFLD, NASH, fibrosis/cirrhosis, and HCC pathogenesis–.

Hepatic alcohol metabolism

37The major type of alcohol that is consumed is ethanol (CH3CH2OH). Upon consumption, ethanol is absorbed via simple diffusion in the small intestine into the blood and rapidly circulates throughout the body. Ethanol metabolism primarily occurs in the liver in three major steps: (1) ethanol oxidation to acetaldehyde, (2) acetaldehyde metabolism to acetate, and (3) acetate catabolism to H2O and CO2–.

38In step I of the hepatic oxidative metabolism of alcohol (ethanol), three distinct enzymes are involved: alcohol dehydrogenase (ADH), catalase, and cytochrome P450-2E1 (CYP2E1). Cytosolic ADH is a major enzyme that catalyzes the oxidative metabolism of ethanol to acetaldehyde by using the cofactor nicotinamide adenine dinucleotide (NAD+) converted to NADH–. Catalase present in peroxisomes may participate in ethanol oxidation in the presence of H2O2–, although this enzyme appears to play no major role in hepatic ethanol metabolism under physiological conditions due to the limited supply of H2O2. After chronic and/or large amounts of ethanol intake, CYP2E1, the major component of the microsomal ethanol oxidizing system (MEOS) with a higher km (~10 mM for ethanol) than that of ADH (km <1 mM for ethanol), is also involved in ethanol metabolism through an NADPH-dependent pathway. In contrast to those of ADH and catalase, CYP2E1 expression and activity are usually induced by ethanol and other substances, such as dietary fats. The induction and activation of CYP2E1, in turn, contribute to alcohol- and nonalcohol-induced pathophysiology–. In the second step, acetaldehyde is converted to acetate due to the low km (for acetaldehyde) mitochondrial aldehyde dehydrogenase 2 isozyme (ALDH2) in humans. Notably, CYP2E1 also takes part in this step with NADPH acting as a cofactor to convert acetaldehyde to acetate. Finally, the acetate that is produced is further degraded to CO2 and H2O, ending the final step of ethanol oxidation in the liver–. Furthermore, the remaining unmetabolized ethanol, acetaldehyde, and acetate can be distributed to many other organs, including the heart, lung, kidney, pancreas, and brain, causing damage in various peripheral tissues and neurobehavioral effects caused by damage to the brain.

Brain alcohol metabolism

39Similar to the liver, ethanol oxidizing enzymes are also functional in the brain and include ADH, catalase, CYP2E1, and ALDH2, which make different contributions. Cerebral ADH plays very little or virtually no role in ethanol metabolism in the brain compared to its action by its hepatic isoform. However, cerebral catalase acts as the main oxidizing enzyme, accounting for more than 60% of ethanol oxidation in the brain under normal conditions. However, catalase may have a limited role in ethanol metabolism in certain brain regions, except for aminergic neurons, where it is present in high concentrations,–. In contrast, CYP2E1 is widely expressed throughout the brain, such as in the cerebral cortex, hippocampus, and cerebellum. Similar to that in the liver, brain CYP2E1 is also inducible by ethanol and may therefore play a key role in cerebral ethanol metabolism, especially after chronic and/or binge alcohol intake–. The role of CYP2E1 in brain ethanol metabolism and its association with alcohol-mediated oxidative neuronal injury– and aging-related AD and PD have also been suggested. Finally, mitochondrial ALDH2 is the final enzyme for converting acetaldehyde to acetate, although acetaldehyde is locally produced in the brain due to its very limited ability to cross the BBB. In contrast, ALDH1B and other isoforms may be involved in acetaldehyde metabolism in rodents,,.

AGE–alcohol–adduct formations (Fig. 1)

40Free amino acid residues of proteins, lipids, nucleic acids, and nucleophilic molecules are major targets of adduct formation or covalent binding with reactive molecules such as acetaldehyde, acrolein, crotonaldehyde, formaldehyde, malondialdehyde, 4-hydroxynonenal, 8-hydroxydeoxyguanosine, N2-((furan-2-yl)methyl)-2′-deoxyguanosine, and N2-ethyl-2′-deoxyguanosine–. After alcohol consumption, CYP2E1 in step I of oxidative ethanol metabolism can generate a series of oxygen free radicals (e.g., ROS) to trigger lipid peroxidation, resulting in the formation of various ethanol metabolites and adducts, including (1) acetaldehyde (AA) from ethanol oxidation, (2) malondialdehyde (MDA) and (3) 4-hydroxynonenal (4-HNE) from lipid peroxidation, (4) malondialdehyde–acetaldehyde adduct (MAA) from the acetaldehyde-MDA-protein hybrid adduct, and (5) hydroxyethyl radicals (HER) from the presence of iron during ethanol metabolism–, although some of these adducts may not be readily detected due to their low levels under physiological conditions.

41MDA and 4-HNE are reactive lipid peroxides with short half-lives that can form covalent adducts with various proteins and nucleic acids in the body. For instance, ethanol intake can induce 4-HNE to interact with cytochrome C oxidase (complex IV) and ALDH2 in the mitochondria, GRP78 and disulfide isomerase in the ER, and ERK1/2, phosphatase and tensin homolog (PTEN), AMP-activated protein kinase (AMPK), and gamma-glutamylcysteine synthetase (GCS) in the cytosol. These adduct formations inactivate their target proteins and result in the accumulation of lipid aldehydes, ER stress, mitochondrial dysfunction, cell signaling alteration, and potentially multitissue injury–.

42Interactions between acetaldehyde or MDA and cellular proteins lead to the formation of MAA adducts, which are highly stable and resistant to rapid degradation,. Increased levels of MAA adducts from alcohol exposure stimulate protein dysfunction and immune-induced tissue injury through interactions with Toll-like receptor-3 (TLR-3), TLR-6, calpain, collagen alpha-1 (XII) chain, procollagen type XIV alpha-1, protocadherin beta, or complement component proteins,.

43Acetaldehyde adducts (AA adducts) are formed by the interaction of acetaldehyde, a direct metabolite of ethanol oxidation and a human carcinogen, with certain amino acids, including lysine, cysteine, and aromatic amino acids. However, these amino acids in different proteins may exert an unequal preference for AA adduct formation. The proteins commonly bound to acetaldehyde to produce AA adducts include membrane proteins of the red blood cells (erythrocytes), hemoglobin (oxygen transport), tubulin (cellular structure), lipoproteins (lipid transport), albumin (blood), and collagen (connective tissue),,. In addition, some of these AA adducts are produced in a CYP2E1-dependent manner,.

44The formation of adduct proteins can prolong protein half-lives and accumulate as aggregated proteins. Since mammalian ubiquitin-dependent proteasomal degradation is usually catalyzed after the conjugation of ubiquitin with lysine residues, it is expected that AA adduct formation and ubiquitin conjugation may compete for common lysine residues. Therefore, when lysine residues are already occupied by reactive acetaldehyde, lipid aldehydes, AGEs, or AA, adducts persist for extended periods of time and may end up as aggregated proteins due to the lack of free lysine needed for ubiquitin conjugation and subsequent proteolysis. In fact, the hypothesis of extended half-lives and aggregations of these adduct proteins is exemplified by the stabilization of CYP2E1 by ethanol and acetone through the blockade of its rapid degradation via ubiquitin-dependent proteolysis–.

45AA adducts are produced in two separate pathways that yield two different types of adducts, depending on the existing conditions. The first pathway is the formation of AA adducts with specific amino acids (lysine, cysteine, or aromatic amino acids) and N-ethyl amino acid groups under reducing conditions. The second is AA adduct synthesis under nonreducing conditions, that creates a wide range of adducts for which the complete mechanisms remain to be further characterized. In the second pathway, the initial step is the formation of a Schiff base adduct followed by several rearrangements and reactions to yield diverse AA adducts.

46Under conditions that include increased lipid peroxidation, such as exposure to alcohol and/or high n-6 fat diets or intake of high fructose drinks, different AGEs are produced by Schiff base formation (Fig. 1). Thus, ethanol and its reactive metabolite, acetaldehyde, are likely involved in the AGE synthesis pathways to produce the final acetaldehyde and AGE (AA-AGE) adducts. The formation of AA-AGE adducts can be observed after chronic alcohol exposure. These AA-AGE adducts exhibit similar properties (e.g., brown color and polymerization) as the AGE adducts cross-link with sugar molecules, and they are distinguished from MAA adducts formed by AA and MDA interactions. Furthermore, treatment with an antioxidant can halt AA-AGE adduct formation, supporting the idea that AA-AGE adducts can be generated from a Schiff base product similar to AA adducts and AGEs.

Brain (see summary in Table 2)

47Chronic and excessive alcohol consumption can alter brain structure and function, causing behavioral, emotional, and intellectual abnormalities. These neurobehavioral changes include the development of alcohol tolerance and addiction, emotional dysregulation, and executive, neurocognitive, and motor dysfunctions with neuroinflammation and/or neurodegeneration. Excessive alcohol exposure increases oxidative stress and the levels of reactive acetaldehyde and lipid aldehydes with a simultaneous decrease in defensive molecules and detoxification enzymes, including GSH and ALDH2,,. These changes subsequently lead to the accumulation of acetaldehyde adducts and possibly AGEs in the brain, which has a much lower detoxification capacity than the liver, as previously mentioned. Additionally, reactive electrophilic acetaldehyde can strongly induce covalent adduct formation with nucleophilic molecules such as proteins and DNA, forming acetaldehyde-protein (AA-protein) or acetaldehyde-DNA (AA-DNA) adducts in the brain–.

48AA-protein adducts are widely present in the brains of alcohol-exposed rodents or people with alcohol use disorder (AUD)–. After alcohol consumption, AA-protein adducts are rapidly produced in the cerebral cortex primarily with mitochondrial proteins and localized in the white matter, deep layers of the frontal cortex, and molecular layer of the cerebellum,,. AA-protein adducts are also formed with cytosolic proteins, including tubulins, known as AA-tubulin adducts, resulting in microtubule malformation and the cytoskeletal dysfunction of nerve cells,. Furthermore, acetaldehyde can interact with dopamine (DA) to produce AA-DA adducts, including salsolinol, a neurotoxin and potent stimulant in alcohol, which is involved in the pathogenesis of AUD and PD,. Additionally, the aggregation of these AA-protein adducts can enhance neuronal damage and degeneration in different brain regions,. These findings suggest a critical role for AA-protein adducts in promoting brain damage and pathophysiology associated with chronic alcohol consumption.

49The presence of acetaldehyde in the brain also alters DNA integrity and neuronal viability. Acetaldehyde can form AA-DNA adducts in the brain and in peripheral blood leukocytes of people with AUD since ethanol, acetaldehyde, and lipid aldehydes such as MDA and 4-HNE can inhibit DNA repair enzymes. The dual mechanisms of simultaneously elevated AA-DNA adducts and suppressed DNA repair systems following alcohol intake may contribute to genetic instability and DNA mutations, promoting neurological pathologies,,.

50In addition to cerebral AA-protein adducts, ethanol intake or exposure can induce and accelerate AGE production in the brain. Aggregation of cross-linked AGEs further upregulates RAGE expression and activation, contributing to diverse outcomes with neurobehavioral impairment, as observed in people with AUD.

51In neurons, direct exposure of AA-AGE adducts to cortical neurons triggers ROS generation, leading to oxidative stress and consequently neuronal apoptosis and degeneration in a dose-dependent manner. These effects can be prevented by treatment with the antioxidant N-acetylcysteine (NAC) or a neutralizing anti-AA-AGE antibody, suggesting a direct role for AA-AGE adducts in generating oxidative stress-induced neurotoxicity. Daily alcohol exposure for ten consecutive days also instigated microglial activation to synthesize and secrete AGE-albumin adducts in the hippocampus and entorhinal cortex of the rat brain. Accumulated AGE-albumin adducts increase the expression of RAGE and activate the MAPK (JNK and p38K)-dependent cell death pathway to promote inflammation, apoptosis, and neuronal damage, which are significantly attenuated by treatment with soluble RAGE and chemical AGE inhibitors. Moreover, ethanol ingestion also upregulates RAGE expression in the orbitofrontal cortex and increases the levels of oxidative stress, HMGB1, TLR-4, neuroimmune markers, and proinflammatory cytokines in the brain. Additionally, chronic exposure to alcohol enhances RAGE expression, ROS generation, nuclear factor erythroid 2–related factor 2 (Nrf2), TLR-4, glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba1), and lipid peroxidation, resulting in neuroinflammation, neuronal apoptosis, and memory impairment. These results strongly suggest a contributing role of the AGE-RAGE axis in alcohol-induced neuroinflammation and neurodegeneration through elevated oxidative stress and upregulated cell death pathways in the brain.

Liver

52Chronic and excessive alcohol intake is known to cause liver injury from mild steatosis (simple fat accumulation in so-called alcoholic fatty liver disease, AFLD) to more advanced liver disease such as inflammation (alcoholic steatohepatitis, ASH), fibrosis/cirrhosis, hepatic cancer, liver failure, and death–. Although many aberrant signaling pathways are found in the pathogenesis of liver diseases, elevated levels of adducts with AA, MDA, MAA, 4-HNE, and HER likely contribute to alcohol-induced cell injury,. After ethanol intake, AA, MDA, and 4-HNE adducts are produced rapidly in the hepatic centrilobular zone (zone III), sinusoids, and HSCs as well as on the hepatocyte surface in the liver. The amounts of these adducts are also markedly elevated in the early phase of alcoholic liver disease (ALD) in the presence or absence of clinical or histological signs–, suggesting their role in the initial development and progression of ALD. In addition to individual AA and MDA adducts, MAA adducts (AA-MDA-protein hybrid adducts) are found in HSCs, liver sinusoidal endothelial cells, and Kupffer cells in ALD models. They also stimulate the transformation of HSCs into activated myofibroblasts, resulting in the elevated production of potent profibrotic factors such as platelet-derived growth factor (PDGF)–. The presence of MAA adducts in these cells can induce proinflammatory cytokines such as TNF-α, IL-12, IL-18, and macrophage migration inhibitory factor (MIF)–. In hepatic Kupffer cells, 4-HNE adducts are also present and activate the infiltration of neutrophils into the liver, leading to the activation of HSCs and an inflammatory cytokine response–. These findings indicate a contributing role of MAA and 4-HNE adducts in promoting the hepatic immune response associated with ALD development. In advanced ALD with cirrhosis, 4-HNE and MDA adducts are also found in greater amounts than in nonalcoholic liver cirrhosis and normal liver,, suggesting the involvement of 4-HNE and MDA adducts in promoting advanced ALD. Finally, adducts derived from HER are also detected in the liver and localized in the microsomes and plasma membranes of hepatocytes and are inducible by alcohol exposure,.

53Ethanol consumption stimulates the formation of AA-AGE in the liver. Increased AA-AGE adduct formation and accumulation were positively correlated with the progression of ALD, as indicated by hepatic fat accumulation and steatohepatitis, which are reversibly ameliorated by alcohol abstinence. HSCs directly exposed to AA-AGE adducts can enhance RAGE expression, ROS generation, and oxidative stress to promote hepatocyte ballooning, apoptosis, and steatosis. These findings suggest a role for AA-AGE adducts in the pathogenesis of AFLD. Alcohol ingestion also enhances AGE synthesis and plasma AGEs in the circulation, especially in the portal and hepatic veins of cirrhotic livers. Elevated AGE levels support AGE-protein adduct formation accompanied by decreased albumin turnover in plasma. Additionally, AGE-protein adducts can accumulate as aggregated proteins in the cells, leading to the activation of Kupffer and HSCs in the liver and microglial cells in the brain followed by parenchymal cell death (e.g., hepatocytes and neurons, respectively), suggesting the involvement of AGEs in the progression of ALD and alcohol-mediated multiorgan injury.

Other organs

54Although more detailed studies need to be conducted, the involvement of AGEs – alcohol –adducts in different cells/tissues is presented as follows:

Lung

55Chronic and/or excessive alcohol intake can cause acute respiratory distress syndrome (ARDS) and other types of pulmonary dysfunction characterized by reduced air exchange rates with increased lung epithelial barrier dysfunction, possibly through increased oxidative stress and MDA and 4-HNE adducts,. Ethanol intake stimulates MAA adduct formation in the lung. Elevated levels of MAA adducts are found in the pulmonary bronchoalveolar lavage fluids obtained from chronically alcohol-exposed animals and in people with AUD,. MAA adducts bind scavenger receptor A (SR-A) on lung macrophages to activate inflammatory processes in airway epithelial cells. The formation of MAA adducts also impedes the wound healing process of bronchial epithelial cells and activates PKC-mediated release of IL-8 in the lung. However, these changes are attenuated by treatment with PKC inhibitors,. In addition to adduct formation, ethanol exposure can increase soluble RAGE expression in bronchoalveolar lavage fluid together with RAGE ligand (HMGB1) in the inflammatory lung,.

Heart

56Excessive alcohol consumption is known to cause cardiac dysfunction with reduced blood ejection force and volume, possibly by augmenting oxidative stress, increasing the levels of MDA and 4-HNE adducts and suppressing ALDH2 activity,. Elevated oxidative stress caused by alcohol oxidation increases acetaldehyde and MDA adduct synthesis in the heart,. However, the contributing roles of AA-MDA adducts in alcohol-mediated myocardiopathy need to be further characterized. Since CYP2E1 and ALDH2 are expressed in the heart, future studies of the opposite regulation of CYP2E1 (i.e., induction) and ALDH2 (i.e., suppression) during the alcohol-mediated production of MDA and/or 4-HNE adducts and the consequent cardiomyopathy would be of interest.

Gut

57Excessive alcohol intake is known to cause leaky gut with increased intestinal cell permeability and endotoxemia, possibly via increased CYP2E1 and oxidative stress–. Ethanol ingestion is likely to increase AA formation in the intestine as a consequence of gut bacteria-mediated alcohol metabolism and the low levels of ALDH2 expression in the gut, although additional studies are needed to extrapolate the roles of these factors in alcohol-mediated gut damage and inflammation. Since CYP2E1 was shown to be involved in the production of hepatic AA- and AA-MDA adducts,,, it would be of interest to study the direct role of CYP2E1 in alcohol-mediated AGE production and GI pathologies.

Pancreas

58Consumption of alcohol enhances the expression of 4-HNE and HER adducts as well as inflammation in the pancreas,. The functional role of these adducts may be related to alcohol-mediated pancreatitis, although this area needs to be evaluated in the future. Since CYP2E1 and ALDH2 are also expressed in the pancreas–, future study of the opposite regulation of CYP2E1 (i.e., induction) and ALDH2 (i.e., inactivation) during the production of MDA and/or 4-HNE adducts and the subsequent damage may be important for understanding the pathogenesis mechanisms of alcohol-mediated pancreatitis and dysfunction.

Serum

59Ethanol intake is known to increase the amounts of MDA adducts and AGEs in the serum. The amounts of MDA adducts are more positively correlated with AGE concentrations than with blood glucose levels. However, the effect of elevated MDA adducts in serum on alcohol-related multiorgan damage needs to be investigated in the future.

Erythrocytes

60After alcohol consumption, AA adducts are produced in blood erythrocytes and are also correlated with the incidence of fetal alcohol spectrum disorders (FASDs),. The pathological mechanisms and implications of these findings need to be evaluated in future studies.

Testis

61Excessive alcohol consumption is known to cause testis dysfunction and degeneration, possibly by increasing oxidative stress. Alcohol intake can induce RAGE overexpression in the testis, whereby RAGE is localized in the interstitial cells and the basal compartment of the seminiferous tubules. Prolonged ethanol exposure stimulates RAGE activation to produce oxidative stress and inflammatory mediators, leading to testicular dysfunction and degeneration. CYP2E1 and ALDH2 are also expressed in the testis,,. Thus, it would be of interest to find the opposite regulations (i.e., induction of CYP2E1 with suppression of ALDH2) and their implications in alcohol-mediated production of MDA and/or 4-HNE adducts and subsequent testis dysfunction.

Translational applications

62We have thus far described the formation of various AGE adducts, interactions with many cellular components, including RAGE, and their pathological implications in aging-related diseases and alcohol-mediated multiorgan damage. Considering the underlying molecular mechanisms of these processes and functional implications, we can suggest a variety of different strategies for use in the effective prevention and therapy of AGE-associated tissue injury and/or RAGE-related diseases. For instance, we can reduce the amounts of potentially harmful AGEs by decreasing the production of endogenous AGEs to prevent many disease states, including aging-related diseases, and by lowering the dietary intake of exogenous AGEs. In fact, decreased intake of n-6 fatty acids in high-fat Western diets, dairy products, and soft drinks with high fructose or sucrose contents in conjunction with increased consumption of n-3 fatty acid-enriched fish and plant-based foods such as legumes, vegetables, fruits, and whole grains are recommended to decrease AGE levels in the body. These healthy dietary choices are consistent with the food recommendations of the American Diabetes Association, the American Heart Association, and the American Institute for Cancer Research–. Many herbs and spices, such as cloves, rosemary, and curcumin, and natural antioxidants, such rice (Oryza sativa L.), and blueberry, exhibit antiglycation activities. These foods are rich in polyphenols such as gallic acid, flavonoids, anthocyanin, and ferulic acid, which attenuate protein glycation and prevent the biosynthesis of AGEs–. As mentioned above, cooking methods can play a critical role in regulating the levels of AGE formation, with effects ranging from those caused by oven-frying > frying > broiling > roasting > boiling/poaching/stewing/steaming. For example, cooking meat (e.g., chicken, pork, or beef) by boiling or stewing can reduce the AGE contents to one-half of that prepared by broiling,. In addition, the water content, cooking method, temperature and time, and food pH are crucial to the final amount of AGEs. Marinating food or meat with acidic ingredients such as lemon juice and vinegar can decrease the amounts of dietary AGEs produced during the high-heat cooking process by as much as 50%. These culinary methods are commonly used for traditional Asian, Mediterranean, and other cuisines worldwide to create palatable and healthy dishes. In addition, changes in behavior or lifestyle, such as decreasing the amount and frequency of alcohol intake and tobacco smoking, and engaging in physical exercise to reduce obesity and diabetes can lower the production of endogenous AGEs, subsequently preventing AGE-associated disease conditions.

63We have also described the roles of increased oxidative stress in promoting the production of AA, MDA, MAA, and other AGE-related adducts and the consequences in aging-related diseases and alcohol-mediated multiorgan damage. In particular, CYP2E1 contributes to the production of AA and MAA adducts, as demonstrated in experimental rodent and cell culture models,,,. Therefore, the inhibition of oxidative stress-producing enzymes such as CYP2E1, and NADPH oxidase is an option to prevent the formation of AGE adducts and AGE-associated cellular and/or organ damage. For instance, taking naturally occurring CYP2E1 inhibitors (e.g., diallyl disulfide in garlic,; phenyl isothiocyanate in cabbage and cruciferous vegetables; ellagic acid in pomegranate; polyunsaturated fatty acids, including docosahexaenoic acid (22:6n-3) and indole-3-carbinol in vegetables and fruits; berberine in fruits and vegetables; walnut; curcumin,; quercetin; and synthetic compounds (chlormethiazole and YH-439,) can prevent alcohol-induced oxidative stress and the formation of various adducts, including AA adducts and AA-MAA adducts,, although the preventive effects of all these dietary compounds on AGE-associated adduct formation have not been specifically evaluated. In addition, dietary AGEs decreased the amounts of SIRT1 and other defensive proteins, including peroxisome proliferator -activated receptor-γ coactivator 1-α (PGC-1α)– and ALDH2. Subchronic alcohol intake also decreased the levels of SIRT1 and PGC-1α and other isoforms,. Thus, activation of SIRT1 by resveratrol and its synthetic structural derivatives, and melatonin may prevent adduct formation and AGE-associated disease conditions. Furthermore, consumption of anti-inflammatory antioxidants from natural dietary supplements,,, and/or synthetic origins can help reduce the incidence and severity of AGE-associated inflammation and related disorders. Furthermore, soluble RAGE,, inhibitors of the RAGE signaling pathway,, neutralizing antibodies against RAGE or AA-AGE adduct, and other AGE-degrading compound(s), such as pyridoxamine and ALT-711, lipoic acid, synthetic compounds OPB-9195, and nitrothiadiazolo[3,2-α]pyrimidines, have been reported to decrease AGE adduct formation. Based on these findings, lifestyle changes that include decreased alcohol consumption, reduced tobacco smoking, and avoidance of potentially harmful diets along with increased physical exercise and daily intake of vegetables and fruits, should be actively promoted and undertaken for proper management of the levels of AGE-related adducts to help prevent aging-related diseases and alcohol-mediated organ damage.

Concluding remarks (see overview in Fig. 2)

64AGEs can be produced endogenously and exogenously. The accumulation of AGEs and the interaction of AGE-RAGE play causative roles in various aging-related diseases and alcohol-mediated tissue injuries by interfering with cell signaling pathways and forming adducts with cellular macromolecules, contributing to their inactivation and pathophysiology in many tissues/organs. These suggest biological connections between AGEs and alcohol adduct formation in relation to alcohol-mediated inflammation, gut leakiness, and multiorgan damage. In addition, the information described in this review can be useful to understand the underlying mechanisms of various diseases caused by alcohol intake, nonalcoholic substances, environmental risk factors, genetic mutations, and aging. These mechanistic insights can serve as a springboard for future translational applications for both the prevention and treatment of diverse disease states.

References 293

1.
Goldberg T, et al. Advanced glycoxidation end products in commonly consumed foods. J. Am. Dietetic Assoc. 2004;104:1287-1291.
Not in our library10.1016/j.jada.2004.05.214
2.
Henning C, Glomb MA. Pathways of the Maillard reaction under physiological conditions. Glycoconj. J. 2016;33:499-512.
Not in our library10.1007/s10719-016-9694-y
3.
Uribarri J, et al. Circulating glycotoxins and dietary advanced glycation endproducts: two links to inflammatory response, oxidative stress, and aging. J. Gerontol. A Biol. Sci. Med Sci. 2007;62:427-433.
Not in our library10.1093/gerona/62.4.427
4.
Byun K, et al. Advanced glycation end-products produced systemically and by macrophages: a common contributor to inflammation and degenerative diseases. Pharmacol. Therapeutics. 2017;177:44-55.
Not in our library10.1016/j.pharmthera.2017.02.030
5.
Abate G, Marziano M, Rungratanawanich W, Memo M, Uberti D. Nutrition and AGE-ing: focusing on Alzheimer’s disease. Oxid. Med. Cell. Longev. 2017;2017:1-10.
Not in our library10.1155/2017/7039816
6.
Jamal, M. et al. in Neuroscience of Alcohol (ed Victor R. Preedy) 39–46 (Academic Press, 2019).
Not in our library
7.
NIAAA. Alcohol Facts and Statistics. The National Institute on Alcohol Abuse and Alcoholism (NIAAA)https://www.niaaa.nih.gov/sites/default/files/AlcoholFactsAndStats.pdf (2020).
Not in our library
8.
Centers for Disease Control and Prevention, Health, United States, With Special Feature on Socioeconomic Status and Health. U.S. Department of Health and Human Services, https://www.cdc.gov/nchs/data/hus/hus11.pdf (2012).
Not in our library
9.
Sacks JJ, Gonzales KR, Bouchery EE, Tomedi LE, Brewer RD. 2010 national and state costs of excessive alcohol consumption. Am. J. preventive Med. 2015;49:e73-e79.
Not in our library10.1016/j.amepre.2015.05.031
10.
Asrani SK, Larson JJ, Yawn B, Therneau TM, Kim WR. Underestimation of liver-related mortality in the United States. Gastroenterology. 2013;145:375-382.e371-372.
Not in our library10.1053/j.gastro.2013.04.005
11.
Ethanol and Cognition: Indirect Effects, Neurotoxicity and Neuroprotection: A Review · 2010
No notice
12.
Rhee SY, Kim YS. The role of advanced glycation end products in diabetic vascular complications. Diabetes Metab. J. 2018;42:188-195.
Not in our library10.4093/dmj.2017.0105
13.
Peppa M, Uribarri J, Vlassara H. Glucose, advanced glycation end products, and diabetes complications: what is new and what works. Clin. Diabetes. 2003;21:186.
Not in our library
14.
Dietary Sugars and Endogenous Formation of Advanced Glycation Endproducts: Emerging Mechanisms of Disease · 2017
No notice
15.
Kikuchi S, et al. Glycation–a sweet tempter for neuronal death. Brain Res. Brain Res. Rev. 2003;41:306-323.
Not in our library10.1016/s0165-0173(02)00273-4
16.
Zhang Q, Ames JM, Smith RD, Baynes JW, Metz TO. A perspective on the Maillard reaction and the analysis of protein glycation by mass spectrometry: probing the pathogenesis of chronic disease. J. Proteome Res. 2009;8:754-769.
Not in our library10.1021/pr800858h
17.
Thornalley PJ. Pharmacology of methylglyoxal: formation, modification of proteins and nucleic acids, and enzymatic detoxification–a role in pathogenesis and antiproliferative chemotherapy. Gen. Pharmacol. 1996;27:565-573.
Not in our library10.1016/0306-3623(95)02054-3
18.
Yan SF, Ramasamy R, Schmidt AM. Mechanisms of disease: advanced glycation end-products and their receptor in inflammation and diabetes complications. Nat. Clin. Pract. Endocrinol. Metab. 2008;4:285-293.
Not in our library10.1038/ncpendmet0786
19.
Dietary Advanced Glycation End Products and Aging · 2010
No notice
20.
Lund MN, Ray CA. Control of Maillard reactions in foods: strategies and chemical mechanisms. J. Agric. Food Chem. 2017;65:4537-4552.
Not in our library10.1021/acs.jafc.7b00882
21.
Nowotny K, Schroter D, Schreiner M, Grune T. Dietary advanced glycation end products and their relevance for human health. Ageing Res. Rev. 2018;47:55-66.
Not in our library10.1016/j.arr.2018.06.005
22.
Delgado-Andrade C. Carboxymethyl-lysine: thirty years of investigation in the field of AGE formation. Food Funct. 2016;7:46-57.
Not in our library10.1039/c5fo00918a
23.
Cerami C, et al. Tobacco smoke is a source of toxic reactive glycation products. Proc. Natl Acad. Sci. USA. 1997;94:13915-13920.
Not in our library10.1073/pnas.94.25.13915
24.
Vlassara H, Uribarri J. Glycoxidation and diabetic complications: modern lessons and a warning? Rev. Endocr. Metab. Disord. 2004;5:181-188.
Not in our library10.1023/b:remd.0000032406.84813.f6
25.
Chan CM, et al. Methylglyoxal induces cell death through endoplasmic reticulum stress-associated ROS production and mitochondrial dysfunction. J. Cell. Mol. Med. 2016;20:1749-1760.
Not in our library10.1111/jcmm.12893
26.
Yamabe S, et al. Intracellular accumulation of advanced glycation end products induces apoptosis via endoplasmic reticulum stress in chondrocytes. FEBS J. 2013;280:1617-1629.
Not in our library10.1111/febs.12170
27.
Kontaxi C, Piccardo P, Gill AC. Lysine-directed post-translational modifications of Tau protein in Alzheimer’s disease and related tauopathies. Front. Mol. Biosci. 2017;4:1-14.
Not in our library10.3389/fmolb.2017.00056
28.
Kuhla B, et al. Effect of pseudophosphorylation and cross-linking by lipid peroxidation and advanced glycation end product precursors on tau aggregation and filament formation. J. Biol. Chem. 2007;282:6984-6991.
Not in our library10.1074/jbc.m609521200
29.
Singh VP, Bali A, Singh N, Jaggi AS. Advanced glycation end products and diabetic complications. Korean J. Physiol. Pharmacol. 2014;18:1-14.
Not in our library10.4196/kjpp.2014.18.1.1
30.
Forbes JM, Cooper ME, Oldfield MD, Thomas MC. Role of advanced glycation end products in diabetic nephropathy. J. Am. Soc. Nephrology: JASN. 2003;14:S254-S258.
Not in our library10.1097/01.asn.0000077413.41276.17
31.
Turner DP. Advanced glycation end-products: a biological consequence of lifestyle contributing to cancer disparity. Cancer Res. 2015;75:1925-1929.
Not in our library10.1158/0008-5472.can-15-0169
32.
Rojas A, Anazco C, Gonzalez I, Araya P. Extracellular matrix glycation and receptor for advanced glycation end-products activation: a missing piece in the puzzle of the association between diabetes and cancer. Carcinogenesis. 2018;39:515-521.
Not in our library10.1093/carcin/bgy012
33.
Genuth S, et al. Skin advanced glycation end products glucosepane and methylglyoxal hydroimidazolone are independently associated with long-term microvascular complication progression of type 1 diabetes. Diabetes. 2015;64:266-278.
Not in our library10.2337/db14-0215
34.
Rondeau P, Bourdon E. The glycation of albumin: structural and functional impacts. Biochimie. 2011;93:645-658.
Not in our library10.1016/j.biochi.2010.12.003
35.
The Receptor for Advanced Glycation End-Products (RAGE) Is Only Present in Mammals, and Belongs to a Family of Cell Adhesion Molecules (CAMs) · 2014
No notice
36.
Choi BR, et al. Increased expression of the receptor for advanced glycation end products in neurons and astrocytes in a triple transgenic mouse model of Alzheimer’s disease. Exp. Mol. Med. 2014;46:1-10.
Not in our library10.1038/emm.2013.147
37.
Chaudhuri J, et al. The role of advanced glycation end products in aging and metabolic diseases: bridging association and causality. Cell Metab. 2018;28:337-352.
Not in our library10.1016/j.cmet.2018.08.014
38.
Wautier M-P, Guillausseau P-J, Wautier J-L. Activation of the receptor for advanced glycation end products and consequences on health. Diabetes Metab. Syndrome: Clin. Res. Rev. 2017;11:305-309.
Not in our library10.1016/j.dsx.2016.09.009
39.
The AGE-RAGE Axis: Implications for Age-Associated Arterial Diseases · 2017
No notice
40.
Xue J, et al. The receptor for advanced glycation end products (RAGE) specifically recognizes methylglyoxal-derived AGEs. Biochemistry. 2014;53:3327-3335.
Not in our library10.1021/bi500046t
41.
Bongarzone S, Savickas V, Luzi F, Gee AD. Targeting the receptor for advanced glycation endproducts (RAGE): a medicinal chemistry perspective. J. Medicinal Chem. 2017;60:7213-7232.
Not in our library10.1021/acs.jmedchem.7b00058
42.
Dhumale SS, Waghela BN, Pathak C. Quercetin protects necrotic insult and promotes apoptosis by attenuating the expression of RAGE and its ligand HMGB1 in human breast adenocarcinoma cells. IUBMB Life. 2015;67:361-373.
Not in our library10.1002/iub.1379
43.
Donato R. RAGE: a single receptor for several ligands and different cellular responses: the case of certain S100 proteins. Curr. Mol. Med. 2007;7:711-724.
Not in our library10.2174/156652407783220688
44.
Jeong J, et al. Soluble RAGE attenuates AngII-induced endothelial hyperpermeability by disrupting HMGB1-mediated crosstalk between AT1R and RAGE. Exp. Mol. Med. 2019;51:1-15.
Not in our library10.1038/s12276-019-0312-5
45.
Miyazaki A, Nakayama H, Horiuchi S. Scavenger receptors that recognize advanced glycation end products. Trends Cardiovasc. Med. 2002;12:258-262.
Not in our library10.1016/s1050-1738(02)00171-8
46.
Ott C, et al. Role of advanced glycation end products in cellular signaling. Redox Biol. 2014;2:411-429.
Not in our library10.1016/j.redox.2013.12.016
47.
Roshandel D, et al. DNA methylation age calculators reveal association with diabetic neuropathy in type 1 diabetes. Clin. Epigenetics. 2020;12:1-16.
Not in our library10.1186/s13148-020-00840-6
48.
Le Bagge, S., Fotheringham, A. K., Leung, S. S. & Forbes, J. M. Targeting the receptor for advanced glycation end products (RAGE) in type 1 diabetes. Med. Res. Rev. 1–20, 10.1002/med.21654 (2020).
Not in our library10.1002/med.21654
49.
Receptor for Advanced Glycation End Products (RAGE) and Mechanisms and Therapeutic Opportunities in Diabetes and Cardiovascular Disease: Insights From Human Subjects and Animal Models · 2020
No notice
50.
Yang P, Feng J, Peng Q, Liu X, Fan Z. Advanced glycation end products: potential mechanism and therapeutic target in cardiovascular complications under diabetes. Oxid. Med. Cell. Longev. 2019;2019:1-12.
Not in our library10.1155/2019/9570616
51.
Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet · 2019
No notice
52.
Lin N, Zhang H, Su Q. Advanced glycation end-products induce injury to pancreatic beta cells through oxidative stress. Diabetes Metab. 2012;38:250-257.
Not in our library10.1016/j.diabet.2012.01.003
53.
Song BJ, et al. Mitochondrial dysfunction and tissue injury by alcohol, high fat, nonalcoholic substances and pathological conditions through post-translational protein modifications. Redox Biol. 2014;3:109-123.
Not in our library10.1016/j.redox.2014.10.004
54.
You J, et al. Advanced glycation end products impair glucose-stimulated insulin secretion of a pancreatic beta-cell line INS-1-3 by disturbance of microtubule cytoskeleton via p38/MAPK activation. J. Diabetes Res. 2016;2016:1-10.
Not in our library10.1155/2016/9073037
55.
Uribarri J, et al. Restriction of advanced glycation end products improves insulin resistance in human type 2 diabetes: potential role of AGER1 and SIRT1. Diabetes Care. 2011;34:1610-1616.
Not in our library10.2337/dc11-0091
56.
Xu J, et al. Involvement of advanced glycation end products in the pathogenesis of diabetic retinopathy. Cell. Physiol. Biochem. 2018;48:705-717.
Not in our library10.1159/000491897
57.
Lim M, et al. Induction of apoptosis of Beta cells of the pancreas by advanced glycation end-products, important mediators of chronic complications of diabetes mellitus. Ann. N. Y. Acad. Sci. 2008;1150:311-315.
Not in our library10.1196/annals.1447.011
58.
Kosmopoulos M, Drekolias D, Zavras PD, Piperi C, Papavassiliou AG. Impact of advanced glycation end products (AGEs) signaling in coronary artery disease. Biochim. Biophys. Acta Mol. Basis Dis. 2019;1865:611-619.
Not in our library10.1016/j.bbadis.2019.01.006
59.
Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation. 2006;114:597-605.
Not in our library10.1161/circulationaha.106.621854
60.
Aleshin A, et al. RAGE modulates myocardial injury consequent to LAD infarction via impact on JNK and STAT signaling in a murine model. Am. J. Physiol. Heart Circ. Physiol. 2008;294:H1823-H1832.
Not in our library10.1152/ajpheart.01210.2007
61.
Tsoporis JN, et al. S100B interaction with the receptor for advanced glycation end products (RAGE): a novel receptor-mediated mechanism for myocyte apoptosis postinfarction. Circ. Res. 2010;106:93-101.
Not in our library10.1161/circresaha.109.195834
62.
The role of advanced glycation end-products in the development of coronary artery disease in patients with and without diabetes mellitus: a review · 2018
No notice
63.
Koska J, et al. Advanced glycation end products, oxidation products, and incident cardiovascular events in patients with type 2 diabetes. Diabetes Care. 2018;41:570-576.
Not in our library10.2337/dc17-1740
64.
Saremi A, et al. Advanced glycation end products, oxidation products, and the extent of atherosclerosis during the va diabetes trial and follow-up study. Diabetes Care. 2017;40:591-598.
Not in our library10.2337/dc16-1875
65.
Fukami K, Taguchi K, Yamagishi S, Okuda S. Receptor for advanced glycation endproducts and progressive kidney disease. Curr. Opin. Nephrol. Hypertension. 2015;24:54-60.
Not in our library10.1097/mnh.0000000000000091
66.
Rabbani N, Thornalley PJ. Advanced glycation end products in the pathogenesis of chronic kidney disease. Kidney Int. 2018;93:803-813.
Not in our library10.1016/j.kint.2017.11.034
67.
Bettiga A, et al. The Modern Western Diet Rich in Advanced Glycation End-Products (AGEs): an overview of its impact on obesity and early progression of renal pathology. Nutrients. 2019;11:E1748.
Not in our library10.3390/nu11081748
68.
Crowley LE, et al. Tissue advanced glycation end product deposition after kidney transplantation. Nephron. Clin. Pract. 2013;124:54-59.
Not in our library10.1159/000355692
69.
Rabbani N, Sebekova K, Sebekova K, Heidland A, Thornalley PJ. Accumulation of free adduct glycation, oxidation, and nitration products follows acute loss of renal function. Kidney Int. 2007;72:1113-1121.
Not in our library10.1038/sj.ki.5002513
70.
Frimat M, et al. Kidney, heart and brain: three organs targeted by ageing and glycation. Clin. Sci. 2017;131:1069-1092.
Not in our library10.1042/cs20160823
71.
Advanced glycation end products mediated cellular and molecular events in the pathology of diabetic nephropathy · 2016
Not checked
72.
Sanajou D, Ghorbani Haghjo A, Argani H, Aslani S. AGE-RAGE axis blockade in diabetic nephropathy: current status and future directions. Eur. J. Pharmacol. 2018;833:158-164.
Not in our library10.1016/j.ejphar.2018.06.001
73.
Cheng M, et al. HMGB1 enhances the AGE-induced expression of CTGF and TGF-beta via RAGE-dependent signaling in renal tubular epithelial cells. Am. J. Nephrol. 2015;41:257-266.
Not in our library10.1159/000381464
74.
Nakamura T, et al. Circulating levels of advanced glycation end products (AGE) and interleukin-6 (IL-6) are independent determinants of serum asymmetric dimethylarginine (ADMA) levels in patients with septic shock. Pharmacol. Res. 2009;60:515-518.
Not in our library10.1016/j.phrs.2009.05.002
75.
Nakamura T, et al. Positive association of serum levels of advanced glycation end products and high mobility group box–1 with asymmetric dimethylarginine in nondiabetic chronic kidney disease patients. Metab. Clin. Exp. 2009;58:1624-1628.
Not in our library10.1016/j.metabol.2009.05.018
76.
Cordova, R. et al. Dietary intake of advanced glycation end products (AGEs) and changes in body weight in European adults. Eur. J. Nutr. 1–12, 10.1007/s00394-019-02129-8 (2019).
Not in our library10.1007/s00394-019-02129-8
77.
Gaens KH, et al. Nepsilon-(carboxymethyl)lysine-receptor for advanced glycation end product axis is a key modulator of obesity-induced dysregulation of adipokine expression and insulin resistance. Arteriosclerosis, Thrombosis, Vasc. Biol. 2014;34:1199-1208.
Not in our library10.1161/atvbaha.113.302281
78.
Sergi, D., Boulestin, H., Campbell, F. M. & Williams, L. M. The role of dietary advanced glycation end products in metabolic dysfunction. Mol. Nutr. Food Res. e1900934, 10.1002/mnfr.201900934 (2020).
Not in our library10.1002/mnfr.201900934
79.
Clarke B. Normal bone anatomy and physiology. Clin. J. Am. Soc. Nephrol. CJASN. 2008;3(Suppl 3):S131-S139.
Not in our library10.2215/cjn.04151206
80.
Okazaki K, et al. Advanced glycation end products (AGEs), but not high glucose, inhibit the osteoblastic differentiation of mouse stromal ST2 cells through the suppression of osterix expression, and inhibit cell growth and increasing cell apoptosis. Calcif. Tissue Int. 2012;91:286-296.
Not in our library10.1007/s00223-012-9641-2
81.
Liu J, et al. AGEs induce apoptosis in rat osteoblast cells by activating the caspase-3 signaling pathway under a high-glucose environment in vitro. Appl. Biochem. Biotechnol. 2016;178:1015-1027.
Not in our library10.1007/s12010-015-1925-3
82.
Zhu SY, et al. Advanced oxidation protein products induce pre-osteoblast apoptosis through a nicotinamide adenine dinucleotide phosphate oxidase-dependent, mitogen-activated protein kinases-mediated intrinsic apoptosis pathway. Aging Cell. 2018;17:1-15.
Not in our library10.1111/acel.12764
83.
Li G, Xu J, Li Z. Receptor for advanced glycation end products inhibits proliferation in osteoblast through suppression of Wnt, PI3K and ERK signaling. Biochem. Biophys. Res. Commun. 2012;423:684-689.
Not in our library10.1016/j.bbrc.2012.06.015
84.
Zhou Z, Xiong W-C. RAGE and its ligands in bone metabolism. Front. Biosci. 2011;3:768-776.
Not in our library10.2741/s185
85.
Lopez-Moreno J, et al. Dietary fat quantity and quality modifies advanced glycation end products metabolism in patients with metabolic syndrome. Mol. Nutr. Food Res. 2017;61:1-12.
Not in our library10.1002/mnfr.201601029
86.
Chen Y, Filipov NM, Guo TL. Dietary glycation products regulate immune homeostasis: early glycation products promote prostate cancer cell proliferation through modulating macrophages. Mol. Nutr. Food Res. 2018;62:1-9.
Not in our library10.1002/mnfr.201700641
87.
Foster D, et al. AGE metabolites: a biomarker linked to cancer disparity? Cancer Epidemiol. Biomark. Prev. 2014;23:2186-2191.
Not in our library10.1158/1055-9965.epi-14-0564
88.
Kang R, et al. The expression of the receptor for advanced glycation endproducts (RAGE) is permissive for early pancreatic neoplasia. Proc. Natl Acad. Sci. USA. 2012;109:7031-7036.
Not in our library10.1073/pnas.1113865109
89.
Nankali M, et al. Increased expression of the receptor for advanced glycation end-products (RAGE) is associated with advanced breast cancer stage. Oncol. Res. Treat. 2016;39:622-628.
Not in our library10.1159/000449326
90.
Pusterla T, et al. Receptor for advanced glycation endproducts (RAGE) is a key regulator of oval cell activation and inflammation-associated liver carcinogenesis in mice. Hepatology. 2013;58:363-373.
Not in our library10.1002/hep.26395
91.
Nguyen AH, Detty SQ, Agrawal DK. Clinical implications of high-mobility group box-1 (HMGB1) and the receptor for advanced glycation end-products (RAGE) in cutaneous malignancy: a systematic review. Anticancer Res. 2017;37:1-7.
Not in our library10.21873/anticanres.11282
92.
Kataoka K, et al. S100A7 promotes the migration and invasion of osteosarcoma cells via the receptor for advanced glycation end products. Oncol. Lett. 2012;3:1149-1153.
Not in our library10.3892/ol.2012.612
93.
Brownlee M. Negative consequences of glycation. Metab. Clin. Exp. 2000;49:9-13.
Not in our library10.1016/s0026-0495(00)80078-5
94.
Su S, Chien M, Lin C, Chen M, Yang S. RAGE gene polymorphism and environmental factor in the risk of oral cancer. J. Dent. Res. 2015;94:403-411.
Not in our library10.1177/0022034514566215
95.
Gentile CL, Weir TL. The gut microbiota at the intersection of diet and human health. Science. 2018;362:776-780.
Not in our library10.1126/science.aau5812
96.
Dinan TG, Cryan JF. Gut-brain axis in 2016: brain-gut-microbiota axis - mood, metabolism and behaviour. Nat. Rev. Gastroenterol. Hepatol. 2017;14:69-70.
Not in our library10.1038/nrgastro.2016.200
97.
Tuohy KM, et al. Metabolism of Maillard reaction products by the human gut microbiota–implications for health. Mol. Nutr. Food Res. 2006;50:847-857.
Not in our library10.1002/mnfr.200500126
98.
Qu W, et al. Dietary advanced glycation end products modify gut microbial composition and partially increase colon permeability in rats. Mol. Nutr. Food Res. 2017;61:1-14.
Not in our library10.1002/mnfr.201700118
99.
Zhao D, et al. Comparison of free and bound advanced glycation end products in food: a review on the possible influence on human health. J. Agric. Food Chem. 2019;67:14007-14018.
Not in our library10.1021/acs.jafc.9b05891
100.
Advanced glycation end products dietary restriction effects on bacterial gut microbiota in peritoneal dialysis patients; a randomized open label controlled trial · 2017
No notice
101.
Alam MZ, Alam Q, Kamal MA, Abuzenadah AM, Haque A. A possible link of gut microbiota alteration in type 2 diabetes and Alzheimer’s disease pathogenicity: an update. CNS Neurol. Disord. Drug Targets. 2014;13:383-390.
Not in our library10.2174/18715273113126660151
102.
de la Monte SM, Kril JJ. Human alcohol-related neuropathology. Acta Neuropathol. 2014;127:71-90.
Not in our library10.1007/s00401-013-1233-3
103.
Srikanth V, et al. Advanced glycation endproducts and their receptor RAGE in Alzheimer’s disease. Neurobiol. Aging. 2011;32:763-777.
Not in our library10.1016/j.neurobiolaging.2009.04.016
104.
Sharma A, et al. Advanced glycation end products and protein carbonyl levels in plasma reveal sex-specific differences in Parkinson’s and Alzheimer’s disease. Redox Biol. 2020;34:101546.
Not in our library10.1016/j.redox.2020.101546
105.
Wang C-Y, et al. Trientine reduces BACE1 activity and mitigates amyloidosis via the AGE/RAGE/NF-κB pathway in a transgenic mouse model of Alzheimer’s disease. Antioxid. Redox Signal. 2013;19:2024-2039.
Not in our library10.1089/ars.2012.5158
106.
Gasparotto J, et al. Systemic inflammation changes the site of RAGE expression from endothelial cells to neurons in different brain areas. Mol. Neurobiol. 2019;56:3079-3089.
Not in our library10.1007/s12035-018-1291-6
107.
Gasparotto J, et al. Receptor for advanced glycation end products mediates sepsis-triggered amyloid-beta accumulation, Tau phosphorylation, and cognitive impairment. J. Biol. Chem. 2018;293:226-244.
Not in our library10.1074/jbc.m117.786756
108.
Byun K, et al. Activated microglial cells synthesize and secrete AGE-albumin. Anat. Cell Biol. 2012;45:47-52.
Not in our library10.5115/acb.2012.45.1.47
109.
Chen K, Maley J, Yu PH. Potential inplications of endogenous aldehydes in beta-amyloid misfolding, oligomerization and fibrillogenesis. J. Neurochem. 2006;99:1413-1424.
Not in our library10.1111/j.1471-4159.2006.04181.x
110.
Wong A, et al. Advanced glycation endproducts co-localize with inducible nitric oxide synthase in Alzheimer’s disease. Brain Res. 2001;920:32-40.
Not in our library10.1016/s0006-8993(01)02872-4
111.
Byun K, et al. Induction of neuronal death by microglial AGE-albumin: implications for Alzheimer’s disease. PloS One. 2012;7:1-11.
Not in our library10.1371/journal.pone.0037917
112.
Bortolotto V, Grilli M. Every cloud has a silver lining: proneurogenic effects of abeta oligomers and HMGB-1 via activation of the RAGE-NF-kappaB axis. CNS Neurol. Disord. Drug Targets. 2017;16:1066-1079.
Not in our library10.2174/1871527315666160803153459
113.
Origlia N, et al. Microglial receptor for advanced glycation end product-dependent signal pathway drives beta-amyloid-induced synaptic depression and long-term depression impairment in entorhinal cortex. J. Neurosci. 2010;30:11414-11425.
Not in our library10.1523/jneurosci.2127-10.2010
114.
Uchiki T, et al. Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in nondiabetics). Aging Cell. 2012;11:1-13.
Not in our library10.1111/j.1474-9726.2011.00752.x
115.
Guerrero E, Vasudevaraju P, Hegde ML, Britton GB, Rao KS. Recent advances in alpha-synuclein functions, advanced glycation, and toxicity: implications for Parkinson’s disease. Mol. Neurobiol. 2013;47:525-536.
Not in our library10.1007/s12035-012-8328-z
116.
Munch G, et al. Crosslinking of alpha-synuclein by advanced glycation endproducts–an early pathophysiological step in Lewy body formation? J. Chem. Neuroanat. 2000;20:253-257.
Not in our library10.1016/s0891-0618(00)00096-x
117.
Sathe K, et al. S100B is increased in Parkinson’s disease and ablation protects against MPTP-induced toxicity through the RAGE and TNF-alpha pathway. Brain J. Neurol. 2012;135:3336-3347.
Not in our library10.1093/brain/aws250
118.
Abdelsalam RM, Safar MM. Neuroprotective effects of vildagliptin in rat rotenone Parkinson’s disease model: role of RAGE-NFkappaB and Nrf2-antioxidant signaling pathways. J. Neurochem. 2015;133:700-707.
Not in our library10.1111/jnc.13087
119.
Bayarsaikhan E, et al. Microglial AGE-albumin is critical for neuronal death in Parkinson’s disease: a possible implication for theranostics. Int. J. Nanomed. 2015;10(Spec Iss):281-292.
Not in our library10.2147/ijn.s95077
120.
Sebekova K, Kupcova V, Schinzel R, Heidland A. Markedly elevated levels of plasma advanced glycation end products in patients with liver cirrhosis - amelioration by liver transplantation. J. Hepatol. 2002;36:66-71.
Not in our library10.1016/s0168-8278(01)00232-x
121.
Development and Progression of Non-Alcoholic Fatty Liver Disease: The Role of Advanced Glycation End Products · 2019
No notice
122.
Sakasai-Sakai A, Takata T, Takino JI, Takeuchi M. Impact of intracellular glyceraldehyde-derived advanced glycation end-products on human hepatocyte cell death. Sci. Rep. 2017;7:1-11.
Not in our library10.1038/s41598-017-14711-3
123.
Gaens KH, et al. Endogenous formation of Nepsilon-(carboxymethyl)lysine is increased in fatty livers and induces inflammatory markers in an in vitro model of hepatic steatosis. J. Hepatol. 2012;56:647-655.
Not in our library10.1016/j.jhep.2011.07.028
124.
Leung C, et al. Dietary glycotoxins exacerbate progression of experimental fatty liver disease. J. Hepatol. 2014;60:832-838.
Not in our library10.1016/j.jhep.2013.11.033
125.
Rolo AP, Teodoro JS, Palmeira CM. Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis. Free Radic. Biol. Med. 2012;52:59-69.
Not in our library10.1016/j.freeradbiomed.2011.10.003
126.
Jiang JX, et al. Advanced glycation endproducts induce fibrogenic activity in nonalcoholic steatohepatitis by modulating TNF-alpha-converting enzyme activity in mice. Hepatology. 2013;58:1339-1348.
Not in our library10.1002/hep.26491
127.
Fehrenbach H, Weiskirchen R, Kasper M, Gressner AM. Up-regulated expression of the receptor for advanced glycation end products in cultured rat hepatic stellate cells during transdifferentiation to myofibroblasts. Hepatology. 2001;34:943-952.
Not in our library10.1053/jhep.2001.28788
128.
Leung C, et al. Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease. World J. Gastroenterol. 2016;22:8026-8040.
Not in our library10.3748/wjg.v22.i35.8026
129.
Hiwatashi K, et al. A novel function of the receptor for advanced glycation end-products (RAGE) in association with tumorigenesis and tumor differentiation of HCC. Ann. Surg. Oncol. 2008;15:923-933.
Not in our library10.1245/s10434-007-9698-8
130.
Takino J, Yamagishi S, Takeuchi M. Glycer-AGEs-RAGE signaling enhances the angiogenic potential of hepatocellular carcinoma by upregulating VEGF expression. World J. Gastroenterol. 2012;18:1781-1788.
Not in our library10.3748/wjg.v18.i15.1781
131.
Yang Y, et al. Pioglitazone, a PPARgamma agonist, inhibits growth and invasion of human hepatocellular carcinoma via blockade of the rage signaling. Mol. Carcinog. 2015;54:1584-1595.
Not in our library10.1002/mc.22231
132.
Purohit V, Gao B, Song BJ. Molecular mechanisms of alcoholic fatty liver. Alcohol. Clin. Exp. Res. 2009;33:191-205.
Not in our library10.1111/j.1530-0277.2008.00827.x
133.
Thiele GM, Klassen LW, Tuma DJ. Formation and immunological properties of aldehyde-derived protein adducts following alcohol consumption. Methods Mol. Biol. 2008;447:235-257.
Not in our library10.1007/978-1-59745-242-7_17
134.
Overview: how is alcohol metabolized by the body? · 2006
No notice
135.
Lieber CS. Microsomal ethanol-oxidizing system (MEOS): the first 30 years (1968-1998)–a review. Alcohol. Clin. Exp. Res. 1999;23:991-1007.
Not in our library
136.
Yun J-W, et al. Binge alcohol promotes hypoxic liver injury through a CYP2E1–HIF-1α-dependent apoptosis pathway in mice and humans. Free Radic. Biol. Med. 2014;77:183-194.
Not in our library10.1016/j.freeradbiomed.2014.08.030
137.
Jeong K-S, et al. Cytochrome P450 2E1 (CYP2E1)-dependent production of a 37-kDa acetaldehyde–protein adduct in the rat liver. Arch. Biochem. Biophys. 2000;384:81-87.
Not in our library10.1006/abbi.2000.2119
138.
Cederbaum AI, Lu Y, Wu D. Role of oxidative stress in alcohol-induced liver injury. Arch. Toxicol. 2009;83:519-548.
Not in our library10.1007/s00204-009-0432-0
139.
Abdelmegeed MA, et al. Critical role of cytochrome P450 2E1 (CYP2E1) in the development of high fat-induced non-alcoholic steatohepatitis. J. Hepatol. 2012;57:860-866.
Not in our library10.1016/j.jhep.2012.05.019
140.
Knockaert L, Descatoire V, Vadrot N, Fromenty B, Robin MA. Mitochondrial CYP2E1 is sufficient to mediate oxidative stress and cytotoxicity induced by ethanol and acetaminophen. Toxicol. Vitro. 2011;25:475-484.
Not in our library10.1016/j.tiv.2010.11.019
141.
Leung TM, Nieto N. CYP2E1 and oxidant stress in alcoholic and non-alcoholic fatty liver disease. J. Hepatol. 2013;58:395-398.
Not in our library10.1016/j.jhep.2012.08.018
142.
Song BJ, Akbar M, Jo I, Hardwick JP, Abdelmegeed MA. Translational implications of the alcohol-metabolizing enzymes, including cytochrome P450-2E1, in alcoholic and nonalcoholic liver disease. Adv. Pharmacol. 2015;74:303-372.
Not in our library10.1016/bs.apha.2015.04.002
143.
Seitz HK. The role of cytochrome P4502E1 in the pathogenesis of alcoholic liver disease and carcinogenesis. Chem. Biol. Interact. 2020;316:108918.
Not in our library10.1016/j.cbi.2019.108918
144.
Song BJ, et al. Contributing roles of CYP2E1 and other cytochrome P450 isoforms in alcohol-related tissue injury and carcinogenesis. Adv. Exp. Med. Biol. 2019;1164:73-87.
Not in our library10.1007/978-3-030-22254-3_6
145.
Klyosov AA, Rashkovetsky LG, Tahir MK, Keung WM. Possible role of liver cytosolic and mitochondrial aldehyde dehydrogenases in acetaldehyde metabolism. Biochemistry. 1996;35:4445-4456.
Not in our library10.1021/bi9521093
146.
Kunitoh S, et al. Acetaldehyde as well as ethanol is metabolized by human CYP2E1. J. Pharmacol. Exp. Therapeutics. 1997;280:527-532.
Not in our library
147.
Zimatkin SM, Pronko SP, Vasiliou V, Gonzalez FJ, Deitrich RA. Enzymatic mechanisms of ethanol oxidation in the brain. Alcohol. Clin. Exp. Res. 2006;30:1500-1505.
Not in our library10.1111/j.1530-0277.2006.00181.x
148.
Deng X-s, Deitrich RA. Putative role of brain acetaldehyde in ethanol addiction. Curr. Drug Abus. Rev. 2008;1:3-8.
Not in our library10.2174/1874473710801010003
149.
Arizzi-LaFrance MN, Correa M, Aragon CM, Salamone JD. Motor stimulant effects of ethanol injected into the substantia nigra pars reticulata: importance of catalase-mediated metabolism and the role of acetaldehyde. Neuropsychopharmacology. 2006;31:997-1008.
Not in our library10.1038/sj.npp.1300849
150.
Zimatkin SM, Lindros KO. Distribution of catalase in rat brain: aminergic neurons as possible targets for ethanol effects. Alcohol Alcohol. 1996;31:167-174.
Not in our library10.1093/oxfordjournals.alcalc.a008128
151.
Hansson T, Tindberg N, Ingelman-Sundberg M, Kohler C. Regional distribution of ethanol-inducible cytochrome P450 IIE1 in the rat central nervous system. Neuroscience. 1990;34:451-463.
Not in our library10.1016/0306-4522(90)90154-v
152.
Yadav S, Dhawan A, Singh RL, Seth PK, Parmar D. Expression of constitutive and inducible cytochrome P450 2E1 in rat brain. Mol. Cell. Biochem. 2006;286:171-180.
Not in our library10.1007/s11010-005-9109-z
153.
Upadhya SC, Tirumalai PS, Boyd MR, Mori T, Ravindranath V. Cytochrome P4502E (CYP2E) in brain: constitutive expression, induction by ethanol and localization by fluorescence in situ hybridization. Arch. Biochem Biophys. 2000;373:23-34.
Not in our library10.1006/abbi.1999.1477
154.
Anandatheerthavarada HK, et al. Induction of brain cytochrome P-450IIE1 by chronic ethanol treatment. Brain Res. 1993;601:279-285.
Not in our library10.1016/0006-8993(93)91721-4
155.
Montoliu C, Valles S, Renau-Piqueras J, Guerri C. Ethanol-induced oxygen radical formation and lipid peroxidation in rat brain: effect of chronic alcohol consumption. J. Neurochem. 1994;63:1855-1862.
Not in our library10.1046/j.1471-4159.1994.63051855.x
156.
Montoliu C, et al. Ethanol increases cytochrome P4502E1 and induces oxidative stress in astrocytes. J. Neurochem. 1995;65:2561-2570.
Not in our library10.1046/j.1471-4159.1995.65062561.x
157.
Brzezinski MR, Boutelet-Bochan H, Person RE, Fantel AG, Juchau MR. Catalytic activity and quantitation of cytochrome P-450 2E1 in prenatal human brain. J. Pharmacol. Exp. Therapeutics. 1999;289:1648-1653.
Not in our library
158.
Haorah J, Knipe B, Leibhart J, Ghorpade A, Persidsky Y. Alcohol-induced oxidative stress in brain endothelial cells causes blood-brain barrier dysfunction. J. Leukoc. Biol. 2005;78:1223-1232.
Not in our library10.1189/jlb.0605340
159.
Zhong Y, et al. Induction of brain CYP2E1 by chronic ethanol treatment and related oxidative stress in hippocampus, cerebellum, and brainstem. Toxicology. 2012;302:275-284.
Not in our library10.1016/j.tox.2012.08.009
160.
Valencia-Olvera AC, Moran J, Camacho-Carranza R, Prospero-Garcia O, Espinosa-Aguirre JJ. CYP2E1 induction leads to oxidative stress and cytotoxicity in glutathione-depleted cerebellar granule neurons. Toxicol. Vitro. 2014;28:1206-1214.
Not in our library10.1016/j.tiv.2014.05.014
161.
Role of Alcohol Drinking in Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis · 2020
No notice
162.
Zimatkin SM. Histochemical study of aldehyde dehydrogenase in the rat CNS. J. Neurochem. 1991;56:1-11.
Not in our library10.1111/j.1471-4159.1991.tb02555.x
163.
Stagos D, et al. Aldehyde dehydrogenase 1B1: molecular cloning and characterization of a novel mitochondrial acetaldehyde-metabolizing enzyme. Drug Metab. Dispos. 2010;38:1679-1687.
Not in our library10.1124/dmd.110.034678
164.
Sapkota M, Wyatt AT. Alcohol, aldehydes, adducts and airways. Biomolecules. 2015;5:2987-3008.
Not in our library10.3390/biom5042987
165.
Sachse B, Meinl W, Glatt H, Monien BH. Ethanol and 4-methylpyrazole increase DNA adduct formation of furfuryl alcohol in FVB/N wild-type mice and in mice expressing human sulfotransferases 1A1/1A2. Carcinogenesis. 2016;37:314-319.
Not in our library10.1093/carcin/bgw006
166.
Wang M, et al. Identification of an acetaldehyde adduct in human liver DNA and quantitation as N2-ethyldeoxyguanosine. Chem. Res Toxicol. 2006;19:319-324.
Not in our library10.1021/tx0502948
167.
Dangerous byproducts of alcohol breakdown--focus on adducts. · 2003
No notice
168.
Freeman TL, et al. Recent advances in alcohol-induced adduct formation. Alcohol. Clin. Exp. Res. 2005;29:1310-1316.
Not in our library10.1097/01.alc.0000171484.52201.52
169.
Worrall S, de Jersey J, Wilce PA. Comparison of the formation of proteins modified by direct and indirect ethanol metabolites in the liver and blood of rats fed the lieber–de carli liquid diet. Alcohol Alcohol. 2000;35:164-170.
Not in our library10.1093/alcalc/35.2.164
170.
Tuma DJ. Role of malondialdehyde-acetaldehyde adducts in liver injury. Free Radic. Biol. Med. 2002;32:303-308.
Not in our library10.1016/s0891-5849(01)00742-0
171.
Niemela O. Aldehyde-protein adducts in the liver as a result of ethanol-induced oxidative stress. Front. Biosci. 1999;4:D506-D513.
Not in our library10.2741/niemela
172.
Doorn JA, Hurley TD, Petersen DR. Inhibition of human mitochondrial aldehyde dehydrogenase by 4-hydroxynon-2-enal and 4-oxonon-2-enal. Chem. Res. Toxicol. 2006;19:102-110.
Not in our library10.1021/tx0501839
173.
Galligan JJ, et al. Oxidative stress-mediated aldehyde adduction of GRP78 in a mouse model of alcoholic liver disease: functional independence of ATPase activity and chaperone function. Free Radic. Biol. Med. 2014;73:411-420.
Not in our library10.1016/j.freeradbiomed.2014.06.002
174.
Sampey BP, Stewart BJ, Petersen DR. Ethanol-induced modulation of hepatocellular extracellular signal-regulated kinase-1/2 activity via 4-hydroxynonenal. J. Biol. Chem. 2007;282:1925-1937.
Not in our library10.1074/jbc.m610602200
175.
Shearn CT, et al. Increased carbonylation of the lipid phosphatase PTEN contributes to Akt2 activation in a murine model of early alcohol-induced steatosis. Free Radic. Biol. Med. 2013;65:680-692.
Not in our library10.1016/j.freeradbiomed.2013.07.011
176.
Shearn CT, Backos DS, Orlicky DJ, Smathers-McCullough RL, Petersen DR. Identification of 5’ AMP-activated kinase as a target of reactive aldehydes during chronic ingestion of high concentrations of ethanol. J. Biol. Chem. 2014;289:15449-15462.
Not in our library10.1074/jbc.m113.543942
177.
Hartley DP, Petersen DR. Co-metabolism of ethanol, ethanol-derived acetaldehyde, and 4-hydroxynonenal in isolated rat hepatocytes. Alcohol. Clin. Exp. Res. 1997;21:298-304.
Not in our library
178.
Tuma DJ, Thiele GM, Xu D, Klassen LW, Sorrell MF. Acetaldehyde and malondialdehyde react together to generate distinct protein adducts in the liver during long-term ethanol administration. Hepatology. 1996;23:872-880.
Not in our library10.1002/hep.510230431
179.
McCaskill ML, et al. Hybrid malondialdehyde and acetaldehyde protein adducts form in the lungs of mice exposed to alcohol and cigarette smoke. Alcohol. Clin. Exp. Res. 2011;35:1106-1113.
Not in our library10.1111/j.1530-0277.2011.01443.x
180.
Patel VB, Worrall S, Emery PW, Preedy VR. Protein adduct species in muscle and liver of rats following acute ethanol administration. Alcohol Alcohol. 2005;40:485-493.
Not in our library10.1093/alcalc/agh196
181.
Swaminathan K, Clemens DL, Dey A. Inhibition of CYP2E1 leads to decreased malondialdehyde-acetaldehyde adduct formation in VL-17A cells under chronic alcohol exposure. Life Sci. 2013;92:325-336.
Not in our library10.1016/j.lfs.2012.12.014
182.
Song BJ. Ethanol-inducible cytochrome P450 (CYP2E1): biochemistry, molecular biology and clinical relevance: 1996 update. Alcohol. Clin. Exp. Res. 1996;20:138a-146a.
Not in our library10.1111/j.1530-0277.1996.tb01764.x
183.
Song BJ, Veech RL, Park SS, Gelboin HV, Gonzalez FJ. Induction of rat hepatic N-nitrosodimethylamine demethylase by acetone is due to protein stabilization. J. Biol. Chem. 1989;264:3568-3572.
Not in our library
184.
Roberts BJ, Shoaf SE, Jeong KS, Song BJ. Induction of CYP2E1 in liver, kidney, brain and intestine during chronic ethanol administration and withdrawal: Evidence that CYP2E1 possesses a rapid phase half-life of 6 hours or less. Biochem. Biophys. Res. Commun. 1994;205:1064-1071.
Not in our library10.1006/bbrc.1994.2774
185.
Abdelmegeed MA, Moon K-H, Chen C, Gonzalez FJ, Song B-J. Role of cytochrome P450 2E1 in protein nitration and ubiquitin-mediated degradation during acetaminophen toxicity. Biochem. Pharmacol. 2010;79:57-66.
Not in our library10.1016/j.bcp.2009.07.016
186.
Roberts BJ, Song BJ, Soh Y, Park SS, Shoaf SE. Ethanol induces CYP2E1 by protein stabilization. Role of ubiquitin conjugation in the rapid degradation of CYP2E1. J. Biol. Chem. 1995;270:29632-29635.
Not in our library10.1074/jbc.270.50.29632
187.
Brooks PJ, Theruvathu JA. DNA adducts from acetaldehyde: implications for alcohol-related carcinogenesis. Alcohol. 2005;35:187-193.
Not in our library10.1016/j.alcohol.2005.03.009
188.
Nakamura K, et al. Immunohistochemical study on acetaldehyde adducts in alcohol-fed mice. Alcohol. Clin. Exp. Res. 2000;24:93s-96s.
Not in our library
189.
Rintala J, et al. Evidence of acetaldehyde-protein adduct formation in rat brain after lifelong consumption of ethanol. Alcohol Alcohol. 2000;35:458-463.
Not in our library10.1093/alcalc/35.5.458
190.
Nakamura K, et al. Acetaldehyde adducts in the brain of alcoholics. Arch. Toxicol. 2003;77:591-593.
Not in our library10.1007/s00204-003-0465-8
191.
Upadhya SC, Ravindranath V. Detection and localization of protein-acetaldehyde adducts in rat brain after chronic ethanol treatment. Alcohol. Clin. Exp. Res. 2002;26:856-863.
Not in our library
192.
Heymann HM, Gardner AM, Gross ER. Aldehyde-induced DNA and protein adducts as biomarker tools for alcohol use disorder. Trends Mol. Med. 2018;24:144-155.
Not in our library10.1016/j.molmed.2017.12.003
193.
Tuma DJ, Smith SL, Sorrell MF. Acetaldehyde and microtubules. Ann. N. Y. Acad. Sci. 1991;625:786-792.
Not in our library10.1111/j.1749-6632.1991.tb33920.x
194.
Smith SL, Jennett RB, Sorrell MF, Tuma DJ. Acetaldehyde substoichiometrically inhibits bovine neurotubulin polymerization. J. Clin. Investig. 1989;84:337-341.
Not in our library10.1172/jci114159
195.
Deehan GA, Hauser SR, Wilden JA, Truitt WA, Rodd ZA. Elucidating the biological basis for the reinforcing actions of alcohol in the mesolimbic dopamine system: the role of active metabolites of alcohol. Front. Behav. Neurosci. 2013;7:1-13.
Not in our library10.3389/fnbeh.2013.00104
196.
Iwahashi, K. et al. [Acetaldehyde adducts in the cerebral cortex of ethanol-fed mice]. Nihon Arukoru Yakubutsu Igakkai zasshi32, 489–494 (1997)..
Not in our library
197.
Lamarche F, Gonthier B, Signorini N, Eysseric H, Barret L. Impact of ethanol and acetaldehyde on DNA and cell viability of cultured neurones. Cell Biol. Toxicol. 2004;20:361-374.
Not in our library10.1007/s10565-004-0087-9
198.
Tong M, et al. Acetaldehyde-mediated neurotoxicity: relevance to fetal alcohol spectrum disorders. Oxid. Med. Cell. Longev. 2011;2011:e213286.
Not in our library
199.
Takeuchi M, et al. Neurotoxicity of acetaldehyde-derived advanced glycation end products for cultured cortical neurons. J. Neuropathol. Exp. Neurol. 2003;62:486-496.
Not in our library10.1093/jnen/62.5.486
200.
Byun K, et al. Microglial AGE-albumin is critical in promoting alcohol-induced neurodegeneration in rats and humans. PloS one. 2014;9:e104699.
Not in our library10.1371/journal.pone.0104699
201.
Vetreno RP, Qin L, Crews FT. Increased receptor for advanced glycation end product expression in the human alcoholic prefrontal cortex is linked to adolescent drinking. Neurobiol. Dis. 2013;59:52-62.
Not in our library10.1016/j.nbd.2013.07.002
202.
Ikram M, et al. Natural dietary supplementation of curcumin protects mice brains against ethanol-induced oxidative stress-mediated neurodegeneration and memory impairment via Nrf2/TLR4/RAGE signaling. Nutrients. 2019;11:E1082.
Not in our library10.3390/nu11051082
203.
Moon KH, et al. Inactivation of oxidized and S-nitrosylated mitochondrial proteins in alcoholic fatty liver of rats. Hepatology. 2006;44:1218-1230.
Not in our library10.1002/hep.21372
204.
Moon KH, et al. Oxidative inactivation of key mitochondrial proteins leads to dysfunction and injury in hepatic ischemia reperfusion. Gastroenterology. 2008;135:1344-1357.
Not in our library10.1053/j.gastro.2008.06.048
205.
Abdelmegeed MA, Moon KH, Hardwick JP, Gonzalez FJ, Song BJ. Role of peroxisome proliferator-activated receptor-alpha in fasting-mediated oxidative stress. Free Radic. Biol. Med. 2009;47:767-778.
Not in our library10.1016/j.freeradbiomed.2009.06.017
206.
Moon KH, Lee YM, Song BJ. Inhibition of hepatic mitochondrial aldehyde dehydrogenase by carbon tetrachloride through JNK-mediated phosphorylation. Free Radic. Biol. Med. 2010;48:391-398.
Not in our library10.1016/j.freeradbiomed.2009.11.008
207.
Diehl AM. Recent events in alcoholic liver disease V. effects of ethanol on liver regeneration. Am. J. Physiol. Gastrointest. Liver Physiol. 2005;288:G1-G6.
Not in our library10.1152/ajpgi.00376.2004
208.
Gao B, Bataller R. Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology. 2011;141:1572-1585.
Not in our library10.1053/j.gastro.2011.09.002
209.
Mandrekar P, Bataller R, Tsukamoto H, Gao B. Alcoholic hepatitis: translational approaches to develop targeted therapies. Hepatology. 2016;64:1343-1355.
Not in our library10.1002/hep.28530
210.
Diehl AM. Developmental morphogens & recovery from alcoholic liver disease. Adv. Exp. Med. Biol. 2018;1032:145-151.
Not in our library10.1007/978-3-319-98788-0_11
211.
Szabo G. Alcoholic liver disease accelerates early hepatocellular cancer in a mouse model. Adv. Exp. Med. Biol. 2018;1032:71-79.
Not in our library10.1007/978-3-319-98788-0_5
212.
Seitz HK, et al. Alcoholic liver disease. Nat. Rev. Dis. Prim. 2018;4:16.
Not in our library10.1038/s41572-018-0014-7
213.
Avila MA, et al. Recent advances in alcohol-related liver disease (ALD): summary of a. Gut Table Meet. Gut. 2020;69:764-780.
Not in our library10.1136/gutjnl-2019-319720
214.
Niemela O, et al. Sequential acetaldehyde production, lipid peroxidation, and fibrogenesis in micropig model of alcohol-induced liver disease. Hepatology. 1995;22:1208-1214.
Not in our library
215.
Hayashi N, et al. Acetaldehyde-derived advanced glycation end-products promote alcoholic liver disease. PloS One. 2013;8:e70034.
Not in our library10.1371/journal.pone.0070034
216.
Niemela O, et al. Early alcoholic liver injury: formation of protein adducts with acetaldehyde and lipid peroxidation products, and expression of CYP2E1 and CYP3A. Alcohol. Clin. Exp. Res. 1998;22:2118-2124.
Not in our library10.1111/j.1530-0277.1998.tb05925.x
217.
Ronis MJ, et al. Increased 4-hydroxynonenal protein adducts in male GSTA4-4/PPAR-alpha double knockout mice enhance injury during early stages of alcoholic liver disease. Am. J. Physiol. Gastrointest. liver Physiol. 2015;308:G403-G415.
Not in our library10.1152/ajpgi.00154.2014
218.
Fritz KS, Petersen DR. Exploring the biology of lipid peroxidation-derived protein carbonylation. Chem. Res Toxicol. 2011;24:1411-1419.
Not in our library10.1021/tx200169n
219.
Shearn CT, Reigan P, Petersen DR. Inhibition of hydrogen peroxide signaling by 4-hydroxynonenal due to differential regulation of Akt1 and Akt2 contributes to decreases in cell survival and proliferation in hepatocellular carcinoma cells. Free Radic. Biol. Med. 2012;53:1-11.
Not in our library10.1016/j.freeradbiomed.2012.04.021
220.
Mello T, Ceni E, Surrenti C, Galli A. Alcohol induced hepatic fibrosis: role of acetaldehyde. Mol. Asp. Med. 2008;29:17-21.
Not in our library10.1016/j.mam.2007.10.001
221.
Wang J-H, Batey R-G, George J. Role of ethanol in the regulation of hepatic stellate cell function. World J. Gastroenterol. 2006;12:6926-6932.
Not in our library10.3748/wjg.v12.i43.6926
222.
Ceni E, Mello T, Galli A. Pathogenesis of alcoholic liver disease: role of oxidative metabolism. World J. Gastroenterol. 2014;20:17756-17772.
Not in our library10.3748/wjg.v20.i47.17756
223.
Willis MS, Klassen LW, Tuma DJ, Sorrell MF, Thiele GM. Adduction of soluble proteins with malondialdehyde-acetaldehyde (MAA) induces antibody production and enhances T-cell proliferation. Alcohol. Clin. Exp. Res. 2002;26:94-106.
Not in our library
224.
Willis MS, Klassen LW, Tuma DJ, Thiele GM. Malondialdehyde-acetaldehyde-haptenated protein induces cell death by induction of necrosis and apoptosis in immune cells. Int. Immunopharmacol. 2002;2:519-535.
Not in our library10.1016/s1567-5769(01)00195-3
225.
Willis MS, Thiele GM, Tuma DJ, Klassen LW. T cell proliferative responses to malondialdehyde-acetaldehyde haptenated protein are scavenger receptor mediated. Int. Immunopharmacol. 2003;3:1381-1399.
Not in our library10.1016/s1567-5769(03)00136-x
226.
Fritz KS, Petersen DR. An overview of the chemistry and biology of reactive aldehydes. Free Radic. Biol. Med. 2013;59:85-91.
Not in our library10.1016/j.freeradbiomed.2012.06.025
227.
Galligan JJ, et al. Protein carbonylation in a murine model for early alcoholic liver disease. Chem. Res. Toxicol. 2012;25:1012-1021.
Not in our library10.1021/tx300002q
228.
Mottaran E, et al. Lipid peroxidation contributes to immune reactions associated with alcoholic liver disease. Free Radic. Biol. Med. 2002;32:38-45.
Not in our library10.1016/s0891-5849(01)00757-2
229.
Moncada C, Torres V, Varghese G, Albano E, Israel Y. Ethanol-derived immunoreactive species formed by free radical mechanisms. Mol. Pharmacol. 1994;46:786-791.
Not in our library
230.
Clot P, et al. Plasma membrane hydroxyethyl radical adducts cause antibody-dependent cytotoxicity in rat hepatocytes exposed to alcohol. Gastroenterology. 1997;113:265-276.
Not in our library10.1016/s0016-5085(97)70104-5
231.
Takeuchi, M.et al. Toxic AGE (TAGE) theory for the pathophysiology of the onset/progression of NAFLD and ALD. Nutrients9, 634 (2017)..
Not in our library10.3390/nu9060634
232.
Ahmed N, et al. Increased protein glycation in cirrhosis and therapeutic strategies to prevent it. Ann. N. Y. Acad. Sci. 2005;1043:718-724.
Not in our library10.1196/annals.1333.083
233.
Grune T. Oxidized protein aggregates: formation and biological effects. Free Radic. Biol. Med. 2020;150:120-124.
Not in our library10.1016/j.freeradbiomed.2020.02.014
234.
Gauthier TW, et al. Fetal alcohol exposure impairs alveolar macrophage function via decreased glutathione availability. Pediatr. Res. 2005;57:76-81.
Not in our library10.1203/01.pdr.0000149108.44152.d3
235.
Sapkota M, et al. Malondialdehyde–acetaldehyde (MAA) protein adducts are found exclusively in the lungs of smokers with alcohol use disorders and are associated with systemic anti-MAA antibodies. Alcohol. Clin. Exp. Res. 2017;41:2093-2099.
Not in our library10.1111/acer.13509
236.
Wyatt TA, Kharbanda KK, Tuma DJ, Sisson JH, Spurzem JR. Malondialdehyde–acetaldehyde adducts decrease bronchial epithelial wound repair. Alcohol. 2005;36:31-40.
Not in our library10.1016/j.alcohol.2005.06.002
237.
Berger JP, et al. Malondialdehyde-acetaldehyde (MAA) adducted proteins bind to scavenger receptor A in airway epithelial cells. Alcohol. 2014;48:493-500.
Not in our library10.1016/j.alcohol.2014.02.005
238.
Duryee MJ, et al. Scavenger receptors on sinusoidal liver endothelial cells are involved in the uptake of aldehyde-modified proteins. Mol. Pharm. 2005;68:1423-1430.
Not in our library10.1124/mol.105.016121
239.
Staitieh BS, Egea EE, Fan X, Amah A, Guidot DM. Chronic alcohol ingestion impairs rat alveolar macrophage phagocytosis via disruption of RAGE signaling. Am. J. Med. Sci. 2018;355:497-505.
Not in our library10.1016/j.amjms.2017.12.013
240.
Harris B, McAlister A, Willoughby T, Sivaraman V. Alcohol-dependent pulmonary inflammation: a role for HMGB-1. Alcohol. 2019;80:45-52.
Not in our library10.1016/j.alcohol.2018.09.008
241.
Chen CH, et al. Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart. Science. 2008;321:1493-1495.
Not in our library10.1126/science.1158554
242.
Zhang Y, Ren J. ALDH2 in alcoholic heart diseases: molecular mechanism and clinical implications. Pharmacol. Therapeutics. 2011;132:86-95.
Not in our library10.1016/j.pharmthera.2011.05.008
243.
Niemela O, Parkkila S, Worrall S, Emery PW, Preedy VR. Generation of aldehyde-derived protein modifications in ethanol-exposed heart. Alcohol. Clin. Exp. Res. 2003;27:1987-1992.
Not in our library10.1097/01.alc.0000099260.58926.f2
244.
Worrall S, Richardson PJ, Preedy VR. Experimental heart muscle damage in alcohol feeding is associated with increased amounts of reduced- and unreduced-acetaldehyde and malondialdehyde-acetaldehyde protein adducts. Addiction Biol. 2000;5:421-427.
Not in our library10.1111/j.1369-1600.2000.tb00211.x
245.
Abdelmegeed MA, et al. CYP2E1 potentiates binge alcohol-induced gut leakiness, steatohepatitis, and apoptosis. Free Radic. Biol. Med. 2013;65:1238-1245.
Not in our library10.1016/j.freeradbiomed.2013.09.009
246.
Forsyth CB, Voigt RM, Keshavarzian A. Intestinal CYP2E1: a mediator of alcohol-induced gut leakiness. Redox Biol. 2014;3:40-46.
Not in our library10.1016/j.redox.2014.10.002
247.
Cho YE, Song BJ. Pomegranate prevents binge alcohol-induced gut leakiness and hepatic inflammation by suppressing oxidative and nitrative stress. Redox Biol. 2018;18:266-278.
Not in our library10.1016/j.redox.2018.07.012
248.
Cho YE, Yu LR, Abdelmegeed MA, Yoo SH, Song BJ. Apoptosis of enterocytes and nitration of junctional complex proteins promote alcohol-induced gut leakiness and liver injury. J. Hepatol. 2018;69:142-153.
Not in our library10.1016/j.jhep.2018.02.005
249.
Salaspuro M. Bacteriocolonic pathway for ethanol oxidation: characteristics and implications. Ann. Med. 1996;28:195-200.
Not in our library10.3109/07853899609033120
250.
Chandrasekaran K, Swaminathan K, Kumar SM, Clemens DL, Dey A. Increased oxidative stress and toxicity in ADH and CYP2E1 overexpressing human hepatoma VL-17A cells exposed to high glucose. Integr. Biol. 2012;4:550-563.
Not in our library10.1039/c2ib00155a
251.
Iimuro Y, et al. Detection of alpha-hydroxyethyl free radical adducts in the pancreas after chronic exposure to alcohol in the rat. Mol. Pharm. 1996;50:656-661.
Not in our library
252.
Casini A, et al. Collagen type I synthesized by pancreatic periacinar stellate cells (PSC) co-localizes with lipid peroxidation-derived aldehydes in chronic alcoholic pancreatitis. J. Pathol. 2000;192:81-89.
Not in our library10.1002/1096-9896(2000)9999:9999<::aid-path675>3.0.co;2-n
253.
Oyama T, et al. Tissue-distribution of aldehyde dehydrogenase 2 and effects of the ALDH2 gene-disruption on the expression of enzymes involved in alcohol metabolism. Front. Biosci. 2005;10:951-960.
Not in our library10.2741/1589
254.
Kimura S, et al. Alcohol and aldehyde dehydrogenase polymorphisms in japanese patients with alcohol-induced chronic pancreatitis. Digestive Dis. Sci. 2000;45:2013-2017.
Not in our library10.1023/a:1005650902961
255.
Vonlaufen A, Wilson JS, Pirola RC, Apte MV. Role of alcohol metabolism in chronic pancreatitis. Alcohol Res. Health. 2007;30:48-54.
Not in our library
256.
Gopal VR, Indira M. Investigations on the correlation of advanced glycated end products (AGE) associated fluorescence with blood glucose and oxidative stress in ethanol-administered diabetic rats. Exp. Toxicol. Pathol. 2010;62:157-162.
Not in our library10.1016/j.etp.2009.03.004
257.
Niemela O, Israel Y. Hemoglobin-acetaldehyde adducts in human alcohol abusers. Lab. Investig. 1992;67:246-252.
Not in our library
258.
Niemelä O, Halmesmäki E, Ylikorkala O. Hemoglobin-acetaldehyde adducts are elevated in women carrying alcohol-damaged fetuses. Alcohol. Clin. Exp. Res. 1991;15:1007-1010.
Not in our library10.1111/j.1530-0277.1991.tb05202.x
259.
Giannessi F, et al. Chronic alcohol administration causes expression of calprotectin and RAGE altering the distribution of zinc ions in mouse testis. Syst. Biol. Reprod. Med. 2015;61:18-25.
Not in our library10.3109/19396368.2014.949905
260.
Healy LN, Pluta LJ, Recio L. Expression and distribution of cytochrome P450 2E1 in B6C3F1 mouse liver and testes. Chem. Biol. Interact. 1999;121:199-207.
Not in our library10.1016/s0009-2797(99)00082-4
261.
Yamauchi M, et al. Association of polymorphism in the alcohol dehydrogenase 2 gene with alcohol-induced testicular atrophy. Alcohol. Clin. Exp. Res. 2001;25:16S-18S.
Not in our library10.1097/00000374-200106001-00005
262.
Lichtenstein AH, et al. Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation. 2006;114:82-96.
Not in our library10.1161/circulationaha.106.176158
263.
Bantle JP, et al. Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association. Diabetes Care. 2008;31(Suppl 1):S61-S78.
Not in our library10.2337/dc08-s061
264.
Glade MJ. Food, nutrition, and the prevention of cancer: a global perspective. American Institute for Cancer Research/World Cancer Research Fund, American Institute for Cancer Research, 1997. Nutrition. 1999;15:523-526.
Not in our library10.1016/s0899-9007(99)00021-0
265.
Premakumara GAS, Abeysekera WKSM, Ratnasooriya WD, Chandrasekharan NV, Bentota AP. Antioxidant, anti-amylase and anti-glycation potential of brans of some Sri Lankan traditional and improved rice (Oryza sativa L.) varieties. J. Cereal Sci. 2013;58:451-456.
Not in our library
266.
Dearlove RP, Greenspan P, Hartle DK, Swanson RB, Hargrove JL. Inhibition of protein glycation by extracts of culinary herbs and spices. J. Med. Food. 2008;11:275-281.
Not in our library10.1089/jmf.2007.536
267.
Yeh WJ, Hsia SM, Lee WH, Wu CH. Polyphenols with antiglycation activity and mechanisms of action: a review of recent findings. J. Food Drug Anal. 2017;25:84-92.
Not in our library10.1016/j.jfda.2016.10.017
268.
Chen H, Virk MS, Chen F. Phenolic acids inhibit the formation of advanced glycation end products in food simulation systems depending on their reducing powers and structures. Int. J. Food Sci. Nutr. 2016;67:400-411.
Not in our library10.3109/09637486.2016.1166187
269.
Evaluation of Polyphenol Anthocyanin-Enriched Extracts of Blackberry, Black Raspberry, Blueberry, Cranberry, Red Raspberry, and Strawberry for Free Radical Scavenging, Reactive Carbonyl Species Trapping, Anti-Glycation, Anti-β-Amyloid Aggregation, and Microglial Neuroprotective Effects · 2018
No notice
270.
Daiponmak W, Senakun C, Siriamornpun S. Antiglycation capacity and antioxidant activities of different pigmented Thai rice. Int. J. Food Sci. Technol. 2014;49:1805-1810.
Not in our library
271.
Sebekova K, Somoza V. Dietary advanced glycation endproducts (AGEs) and their health effects–PRO. Mol. Nutr. Food Res. 2007;51:1079-1084.
Not in our library10.1002/mnfr.200700035
272.
Uribarri J, et al. Advanced glycation end products in foods and a practical guide to their reduction in the diet. J. Am. Dietetic Assoc. 2010;110:911-916.e912.
Not in our library10.1016/j.jada.2010.03.018
273.
Swaminathan K, Kumar SM, Clemens DL, Dey A. Inhibition of CYP2E1 leads to decreased advanced glycated end product formation in high glucose treated ADH and CYP2E1 over-expressing VL-17A cells. Biochim. Biophys. Acta. 2013;1830:4407-4416.
Not in our library10.1016/j.bbagen.2013.05.022
274.
Kimura Y, et al. Atorvastatin decreases serum levels of advanced glycation endproducts (AGEs) in nonalcoholic steatohepatitis (NASH) patients with dyslipidemia: clinical usefulness of AGEs as a biomarker for the attenuation of NASH. J. Gastroenterol. 2010;45:750-757.
Not in our library10.1007/s00535-010-0203-y
275.
Morimoto M, et al. Modulation of experimental alcohol-induced liver disease by cytochrome P450 2E1 inhibitors. Hepatology. 1995;21:1610-1617.
Not in our library
276.
Yoshigae Y, Sridar C, Kent UM, Hollenberg PF. The inactivation of human CYP2E1 by phenethyl isothiocyanate, a naturally occurring chemopreventive agent, and its oxidative bioactivation. Drug Metab. Dispos. 2013;41:858-869.
Not in our library10.1124/dmd.112.050609
277.
Song BJ, Moon KH, Olsson NU, Salem N. Prevention of alcoholic fatty liver and mitochondrial dysfunction in the rat by long-chain polyunsaturated fatty acids. J. Hepatol. 2008;49:262-273.
Not in our library10.1016/j.jhep.2008.04.023
278.
Choi Y, Abdelmegeed MA, Song BJ. Preventive effects of indole-3-carbinol against alcohol-induced liver injury in mice via antioxidant, anti-inflammatory, and anti-apoptotic mechanisms: role of gut-liver-adipose tissue axis. J. Nutr. Biochem. 2018;55:12-25.
Not in our library10.1016/j.jnutbio.2017.11.011
279.
Zhang P, et al. Demethyleneberberine, a natural mitochondria-targeted antioxidant, inhibits mitochondrial dysfunction, oxidative stress, and steatosis in alcoholic liver disease mouse model. J. Pharmacol. Exp. Therapeutics. 2015;352:139-147.
Not in our library10.1124/jpet.114.219832
280.
Choi Y, Abdelmegeed MA, Song BJ. Preventive effects of dietary walnuts on high-fat-induced hepatic fat accumulation, oxidative stress and apoptosis in mice. J. Nutr. Biochem. 2016;38:70-80.
Not in our library10.1016/j.jnutbio.2016.08.013
281.
Luo DD, et al. Tetrahydrocurcumin and octahydrocurcumin, the primary and final hydrogenated metabolites of curcumin, possess superior hepatic-protective effect against acetaminophen-induced liver injury: role of CYP2E1 and Keap1-Nrf2 pathway. Food Chem. Toxicol. 2019;123:349-362.
Not in our library10.1016/j.fct.2018.11.012
282.
Lee HI, et al. Low doses of curcumin protect alcohol-induced liver damage by modulation of the alcohol metabolic pathway, CYP2E1 and AMPK. Life Sci. 2013;93:693-699.
Not in our library10.1016/j.lfs.2013.09.014
283.
Ma JQ, Luo RZ, Jiang HX, Liu CM. Quercitrin offers protection against brain injury in mice by inhibiting oxidative stress and inflammation. Food Funct. 2016;7:549-556.
Not in our library10.1039/c5fo00913h
284.
Gebhardt AC, Lucas D, Menez JF, Seitz HK. Chlormethiazole inhibition of cytochrome P450 2E1 as assessed by chlorzoxazone hydroxylation in humans. Hepatology. 1997;26:957-961.
Not in our library10.1002/hep.510260423
285.
Zimmerman MC, et al. Direct antioxidant properties of methotrexate: inhibition of malondialdehyde-acetaldehyde-protein adduct formation and superoxide scavenging. Redox Biol. 2017;13:588-593.
Not in our library10.1016/j.redox.2017.07.018
286.
Lieber CS, Leo MA, Wang X, Decarli LM. Effect of chronic alcohol consumption on Hepatic SIRT1 and PGC-1alpha in rats. Biochem. Biophys. Res. Commun. 2008;370:44-48.
Not in our library10.1016/j.bbrc.2008.03.005
287.
Lieber CS, Leo MA, Wang X, Decarli LM. Alcohol alters hepatic FoxO1, p53, and mitochondrial SIRT5 deacetylation function. Biochem. Biophys. Res. Commun. 2008;373:246-252.
Not in our library10.1016/j.bbrc.2008.06.006
288.
Bonkowski MS, Sinclair DA. Slowing ageing by design: the rise of NAD(+) and sirtuin-activating compounds. Nat. Rev. Mol. Cell Biol. 2016;17:679-690.
Not in our library10.1038/nrm.2016.93
289.
Dai H, Sinclair DA, Ellis JL, Steegborn C. Sirtuin activators and inhibitors: promises, achievements, and challenges. Pharm. Ther. 2018;188:140-154.
Not in our library10.1016/j.pharmthera.2018.03.004
290.
Lee SE, et al. Induction of SIRT1 by melatonin improves alcohol-mediated oxidative liver injury by disrupting the CRBN-YY1-CYP2E1 signaling pathway. J. Pineal Res. 2020;68:1-15.
Not in our library10.1111/jpi.12638
291.
Munch G, Kuhla B, Luth HJ, Arendt T, Robinson SR. Anti-AGEing defences against Alzheimer’s disease. Biochemical Soc. Trans. 2003;31:1397-1399.
Not in our library10.1042/bst0311397
292.
Tsuchida K, et al. Suppression of transforming growth factor beta and vascular endothelial growth factor in diabetic nephropathy in rats by a novel advanced glycation end product inhibitor, OPB-9195. Diabetologia. 1999;42:579-588.
Not in our library10.1007/s001250051198
293.
Savateev K, et al. Nitrothiadiazolo[3,2-a]pyrimidines as promising antiglycating agents. Eur. J. Med. Chem. 2020;185:1-11.
Not in our library10.1016/j.ejmech.2019.111808

Cited by papers we hold 8

Contributing roles of mitochondrial dysfunction and hepatocyte apoptosis in liver diseases through oxidative stress, post-translational modifications, inflammation, and intestinal barrier dysfunction · 2024
No notice
Antioxidants in Alzheimer’s Disease: Current Therapeutic Significance and Future Prospects · 2022
No notice
Advanced Glycation End-Products (AGEs): Formation, Chemistry, Classification, Receptors, and Diseases Related to AGEs · 2022
No notice
Inflammation in Metabolic Cardiomyopathy · 2021
Not checked
Narcolepsy in Parkinson's disease with insulin resistance [version 2; peer review: 1 approved, 2 approved with reservations] · 2021
Not checked
Human Tau Isoforms and Proteolysis for Production of Toxic Tau Fragments in Neurodegeneration · 2021
Not checked
Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery · 2021
No notice
Skin Wound Healing: Normal Macrophage Function and Macrophage Dysfunction in Diabetic Wounds · 2021
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.