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Iron Metabolism, Ferroptosis, and the Links With Alzheimer’s Disease

Nao Yan, JunJian Zhang

Frontiers in Neuroscience · 2020 · Review · CC BY

doi:10.3389/fnins.2019.01443

Abstract

Iron is an essential transition metal for numerous biologic processes in mammals. Iron metabolism is regulated via several coordination mechanisms including absorption, utilization, recycling, and storage. Iron dyshomeostasis can result in intracellular iron retention, thereby damaging cells, tissues, and organs through free oxygen radical generation. Numerous studies have shown that brain iron overload is involved in the pathological mechanism of neurodegenerative disease including Alzheimer's disease (AD). However, the underlying mechanisms have not been fully elucidated. Ferroptosis, a newly defined iron-dependent form of cell death, which is distinct from apoptosis, necrosis, autophagy, and other forms of cell death, may provide us a new viewpoint. Here, we set out to summarize the current knowledge of iron metabolism and ferroptosis, and review the contributions of iron and ferroptosis to AD.

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From PubMed Central, U.S. National Library of Medicine, as current on Oct 20, 2026. Paragraph numbers are ours, so an answer can point at one.

Introduction

Iron is the second most abundant metal of the earth’s crust following aluminum and the most abundant transition metal in biology. Iron plays a crucial role in various vital biological processes by different oxidation states, including oxygen transportation, DNA synthesis and repair, respiratory activity, myelin synthesis, and cellular metabolism. Iron homeostasis is maintained via multiple mechanisms such as hepcidin and iron regulatory proteins (IRPs) at the systemic and cellular levels. Disruption of iron homeostasis can result in excessive intracellular iron accumulation, thereby damaging proteins, lipids, and DNA via generation of free radicals and oxidative stress.

Accumulating studies have shown that iron dyshomeostasis is involved in the pathogenesis of Alzheimer’s disease (AD). Iron depositions in the specific brain regions have been proved in AD through imaging and histologic examinations. Ferroptosis is a newly non-apoptotic form of cell death, which is characterized by the iron-dependent accumulation of lipid reactive oxygen species (ROS). Recent studies show that ferroptosis plays a key role in neuronal death and neurological diseases including traumatic brain injury (TBI), stroke, Friedreich’s ataxia, AD, Parkinson’s disease (PD), and Huntington’s disease (HD). These studies provide us novel perspectives. Hence, we summarize the current knowledge of iron metabolism and ferroptosis, and review the contributions of iron and ferroptosis to AD.

Brain Iron Metabolism

Iron is a vital element for a myriad of fundamental biological functions, because it can readily donate and accept electrons to participate in oxidation–reduction reactions. But it is also toxic when excess “free” iron is present. Indeed, this redox-active iron can catalyze the production of ROS by Fenton reaction, thereby attacking cellular lipids, proteins, and nucleic acids and causing cell damage. Iron plays a crucial role in the synthesis of myelin and neurotransmitters in the central nervous system. However, excessive brain iron concentrations are thought to be a potential cause for various neurodegenerative diseases including AD, PD, HD, and multiple sclerosis. And iron deficiency in infants and the developing brain can easily cause neurological deficits and mental retardation. Accordingly, iron metabolism must be elegantly regulated by a complex network of processes including absorption, utilization, recycling, and storage. This complex, highly regulated process involves a series of proteins such as ferritin (FTH1), transferrin (Tf), transferrin receptor 1 (TfR1), divalent metal transporter 1 (DMT1, SLC11A2), ferroportin (FPN1), and hepcidin.

The blood–brain barrier (BBB) is the unique structure in the brain that is different from other tissues and organs, which tightly regulates the movement of ions, molecules, and cells between the blood and the brain. Thus, the endothelial cells of the BBB are the key site for regulating brain iron uptake, and the Tf/TfR1 pathway is the main brain iron absorption route depending on BBB. Research shows that Tf is the iron carrier that is responsible for delivering ferric iron to erythrocyte precursors and other tissues, but the ferrous iron must be oxidized to ferric iron by hephestin, a multi-copper ferroxidase enzyme, before it binds to Tf. TfR1 is highly expressed on the luminal side of endothelial cells. Accordingly, Tf-bound serum iron in circulation binds to its receptor (TfR1) firstly, and Tf/TfR1 complex is taken up through endocytosis; then ferric iron is released from Tf, and ferric iron is reduced to ferrous iron by ferric reductase six-transmembrane epithelial antigen of prostate 3 (STEAP3) in the acidic endosome, thereby transferring by DMT1 for metabolic synthesis or for storage with ferritin in the cytoplasm. DMT1 is a metal transporter that principally transports iron from the endosome to cytoplasm. Furthermore, iron could also be exported by FPN1 to the extracellular environment. FPN1 is the sole known intracellular iron exporter in mammals, which plays a vital role in the export of cellular iron. And FPN1is controlled by the iron-regulatory hormone hepcidin, which is mainly synthesized and secreted by hepatocytes. Hepcidin binds directly to FPN1 and triggers its internalization, ubiquitination, and degradation. Ultimately, iron across the BBB can be absorbed by neurons, microglia, and astrocytes via the same iron metabolism-related proteins.

But different cell types have different ways of iron absorption. Neurons and microglia can acquire iron by means of the Tf/TfR1 pathway or absorb non-Tf-bound iron (NTBI) via the luminal DMT1-dependent pathway. Recent studies show that the binding of H-ferritin to the H-ferritin receptor (Tim-1/2) may be the major source of iron uptaking for oligodendrocytes. In addition to the Tf/TfR1 or DMT1 pathway, astrocytes may acquire iron by their end-feet processes. In this way, brain iron levels are precisely regulated to participate in normal neuronal function.

Ferroptosis and Iron

Ferroptosis is a novel defined form of regulated cell death, which is characterized by iron-dependent lipid peroxidation that ultimately leads to oxidative stress and cell death. Ferroptotic cell death is morphologically, biochemically, and genetically distinguished from other forms of cell death including apoptosis, necrosis, autophagy, and pyroptosis. In cytological changes, the chief distinguishing features of ferroptosis are decreased or vanished mitochondria cristae, condensed mitochondrial membrane, and mitochondria volume shrinkage. The hallmark of ferroptosis is accumulation of iron-dependent ROS, reduction of glutathione (GSH) level, and inactivation of glutathione peroxidase 4 (GPX4); thereby this redox dyshomeostasis triggers cell death. Intracellular iron accumulation can generate ROS and cause oxidative stress via Fenton reaction, thereby promoting the peroxidation of proteins, nucleic acids, and lipids, which is the key process to propagate ferroptosis. Interestingly, ferroptosis inducers were firstly found before the term ferroptosis was coined. To start with, researchers unexpectedly found that the small molecule erastin induced non-apoptotic cell death in tumorigenic cells. Afterward, two ras-selective lethal small molecular compounds (RSL3 and RSL5) were screened out that induced non-apoptotic and iron-dependent oxidative cell death. And an iron chelator (desferrioxamine) and an antioxidant (vitamin E) could prevent this form of cell death, which showed similar properties with previous cell death form induced by erastin. Thus, ferroptosis was named for this novel non-apoptotic cell death in 2012, which suggests that redox-active iron plays a critical role in this novel cell death mechanism.

Although the exact mechanisms of iron in the signaling pathway of ferroptosis are still poorly understand, the involvement of iron dyshomeostasis in the ferroptotic process is beyond any doubt. Indeed, lipid peroxidation and lethal ROS resulting from iron-mediated Fenton reaction or enzymatic oxygenation is the essential step of ferroptosis. Iron homeostasis is a complex process and relies on coordination of multiple iron metabolism proteins. Once the expression of these molecules is altered, ferroptosis may be triggered. Recent research found that the iron-carrier serum protein Tf and its cell surface receptor, TfR1, played critical roles in ferroptotic cell demise. The Tf/TfR1 pathway is mainly responsible for the absorption of cell iron. And abnormal TfR1 recycling and palmitoylation can result in neurodegeneration with brain iron accumulation (NBIA). The DMT1, another important iron-absorbing protein, is also closely associated with brain iron accumulation in neurodegenerative diseases. Multiple studies have shown that DMT1 overexpression contributed to iron accumulation in the substantia nigra and dopaminergic neuron loss. Ferritin is the main intracellular iron storage protein composed of FTL1 (light chains) and FTH1 (ferritin heavy), which preserves excess iron in a redox inactive form and prevents the cell and tissue from oxidative damage. Nuclear receptor coactivator 4 (NCOA4) is a selective cargo receptor, which is responsible for binding to ferritin and transporting it to the lysosome for degradation. Thus, this process is termed ferritinophagy, and NCOA4-mediated ferritinophagy induces ferroptosis by degradation of ferritin and increasing cellular labile iron levels. Indeed, abnormal iron balance caused by dysfunctional ferritinophagy is critical to induce ferroptosis and also plays a central role in neurodegenerative diseases mediated by ferroptosis. The mechanisms of iron overload in ferroptosis are not well understood partly because of the difficulty of measurement. Investigators currently have designed a unique fluorescence resonance energy transfer (FRET) probe, FRET Iron Probe 1 (FIP-1), which provides direct evidence for changes in labile iron status during ferroptosis.

Furthermore, iron is also an important component that composes a subunit of oxidase for lipid peroxidation. Lipoxygenases (LOXs) are a family of non-heme iron enzymes, which can drive ferroptosis by peroxidation of cellular membrane polyunsaturated fatty acids (PUFAs). The iron in LOX active sites plays an important role in generating toxic lipid hydroperoxides. And the iron chelators (deferoxamine and deferiprone) also could rescue ferroptosis through removing the essential catalytic iron from LOXs. Recent studies show that arachidonate-15-lipoxygenase (ALOX15) plays a significant role in erastin-induced ferroptosis by facilitating the formation of lipid peroxides. And intracellular iron accumulation and lipid peroxidation are two key events initiating ferroptosis. Iron not only directly catalyzes the formation of ROS, but also synthesizes the LOXs that oxidize PUFAs to result in lipid peroxides in ferroptosis. Altogether, iron is the essential component of ferroptosis.

Iron Metabolism Linking With AD Pathology

Alzheimer’s disease is considered currently as a complicated neurodegenerative disease with multiple cerebral pathologies. The most typical histopathological features of AD are the deposition of extracellular amyloid-β (Aβ) in senile plaques (SPs) and intracellular neurofibrillary tangles (NFTs) formed by hyperphosphorylation of tau protein. These changes of nerve cells are ultimately accompanied by dead and dying neurons. Many studies have shown that brain iron dyshomeostasis is tightly associated with Aβ plaques and NFTs. Indeed, iron deposition has been involved in the two misfolding process. SP and NFT complexes cover redox-active transition metals.

Aβ precursor protein (APP) is a type 1 transmembrane glycoprotein, which is the crucial precursor to the production of Aβ. APP can undergo proteolytic cleavage first by α-secretase or β-secretase and then γ-secretase. In health, α-secretase firstly cleaving APP means being on the non-amyloidogenic pathway. However, once APP is cleaved first by the β-secretase enzyme, it finally can produce the neurotoxic 40- to 42-amino-acid amyloid (the amyloidogenic pathway). And furin plays a key role in mediating the proteolytic activation ratio of α-secretase or β-secretase. Indeed, the concentration of furin protein was positively correlated with α-secretase activity and negatively correlated with β-secretase activity. Excessive intracellular iron concentration is responsible for reducing transcriptional regulation of furin. And iron can reinforce the β-secretase activity by the decrease of furin protein, thereby directly increasing Aβ production by the amyloidogenic pathway. Furthermore, APP mRNA encodes iron-responsive elements (IREs) in the 5’-untranslated region (5’-UTR mRNA), which is closely related to intracellular iron content. When the intracellular iron concentrations increase, it upregulates the translation of APP by virtue of IREs in the 5’-UTR mRNA, thereby increasing the amount of APP protein and potentially producing more Aβ. Additionally, iron also directly binds to Aβ in His6, His13, and His14 amino acid residues, thereby strengthening the neurotoxicity of Aβ.

Indeed, it is widely accepted that APP also physically interacts with the cell surface FPN1 through stabilizing and locating FPN1, and enabling intracellular iron efflux. Recent research indicates that brain FPN1 levels reduce brain iron accumulation in APP-KO mice, and the ability of cerebral iron export was significantly decreased, which reveals that APP/FPN1 plays a crucial role in modulating cerebral iron homeostasis. New research shows that post-translational modulation plays a key role in locating and trafficking of APP to the cell surface. The study confirmed that damaged N-glycosylation or phosphorylation of APP impeded the trafficking of APP to the cell surface, which disturbed FPN1 stability and reduced cell surface FPN1 levels, thereby altering neuronal iron homeostasis and resulting in intracellular iron retention. Meanwhile, Post-translational modifications of APP induced conformation changes and altered the cleavage preference of each secretase, thereby dysregulating APP processing and Aβ generation. Indeed, there is also a study that shows that iron accumulation induces binding of APP to β-secretase, thereby resulting in Aβ accumulation (the amyloidogenic pathway), and reduces the affinity of APP/FPN1 mediating iron export in microglia. Furthermore, synchrotron X-ray spectromicroscopy technology also shed light on the presence of ferrous iron (redox-active iron phases) in amyloid plaque cores. The research indicates that Aβ plays a important role in reducing ferric iron into ferrous forms; this transformation process leads to excess free radical generation and inducing neuronal damage, which could promote the understanding of the role of iron in the pathology of AD.

Neuroinflammatory response and microglial activation also are the typical changes of AD pathogenesis. Recent studies have shown that iron accumulation in microglia also contributes to microglial dysfunction and Aβ accumulation. In APP/PS1 mice, a commonly used animal model of AD, which overexpresses the APP and presenilin 1 (PS1), the researcher attests that iron accumulation can drive microglia to switch to a glycolytic metabolic, thereby reducing the capacity to phagocytose Aβ, ultimately leading to Aβ accumulation. And microglia has two polarization states with opposite functions including M1 proinflammatory, cytotoxic cell type and anti-inflammatory, prorepair M2 cell type. M1 phenotype microglia plays an important role in the pro-inflammatory response. Recent research shows that iron accumulation can drive microglia polarization to M1 phenotype. And it was found out that there is a large amount of activated iron-containing microglia around Aβ plaques. Additionally, cortical iron deposition is increasingly recognized as a novel imaging marker for AD diagnosis through using high field magnetic resonance imaging (MRI) to scan hemispheres of AD patients. And cerebral quantitative susceptibility mapping (QSM), an MRI method sensitive to brain iron, reveals that the brain iron burden is elevated in AD patients, combined with Aβ positron emission tomography (PET), which indicates that brain iron load is positively associated with Aβ deposition-related cognitive decline, suggesting that iron may combine with Aβ to exacerbate the cognitive function damage. The pathologic mechanism could be that iron promotes the production of free radicals and oxidative stress and possibly also involves ferroptosis. And other research validates that spatial colocalization of cerebral iron with Aβ plaques increased the risk for AD dementia. Moreover, in mild and moderate AD patients, the researchers determined the magnetic susceptibility values of deep gray matter nuclei with QSM and evaluated the cognitive functions through Montreal cognitive assessment (MoCA) and mini-mental state examination (MMSE). They found that the magnetic susceptibility of the left caudate nucleus was significantly correlated with the severity of cognitive questionnaire scores (MMSE and MoCA) in AD. Altogether, these studies indicate that it is possible for brain iron levels quantified by QSM to be a biomarker of the severity of AD.

Ferritin is the major iron storage protein, and cerebrospinal fluid (CSF) ferritin could reflect cerebral iron levels. Studies have shown that CSF ferritin can be recognized as a potential biomarker, which is better to predict disease progression and future cognitive impairment, especially in patients with high Aβ deposition or APOE-ε4 carriers. And high CSF ferritin levels in the presence of Aβ accumulation indicate a high risk of brain hypometabolism and cognitive decline. It is generally accepted that APOE-ε4 is the greatest genetic risk for AD. And research shows that APOE-4 could intervene in brain iron homeostasis by increasing ferritin levels, thereby strengthening the susceptibility to AD. These findings also indicate that CSF ferritin has the potential to be a biomarker of AD and highlight the role of iron in the AD pathological mechanism.

Under physiological conditions, tau is a microtubule-associated protein that supports neuronal microtubule structure, which plays a key role in axonal transport, protein trafficking, and cognitive function. However, tau hyperphosphorylation aggregates into NFTs, which is a major pathological hallmark of AD. And it is widely believed that brain iron dyshomeostasis is closely associated with the formation of NFTs and the progression of tau-mediated neurodegeneration. Iron not only can regulate tau phosphorylation but also can induce the aggregation of hyperphosphorylated tau. Indeed, iron deposition is colocalized with NFTs in a special brain region associated with the progression of neurodegeneration. Furthermore, many proline-directed protein kinases are also closely interrelated with tau phosphorylation in AD such as glycogen synthase kinase-3 (GSK3), cyclin-dependent protein kinase-5 (CDK5), and mitogen-activated protein kinases (MAPKs). Indeed, excess neuronal iron can promote tau hyperphosphorylation and facilitate the formation of NFTs through cyclin-dependent kinase (CDK5)/P25 complex and GSK-3β kinase pathways. Additionally, the study also shows that dysfunctional insulin signaling is associated with iron-induced abnormal phosphorylation of tau in AD.

Research shows that tau plays an important role in protein trafficking via stabilizing neuronal microtubules. And tau can mediate cellular iron efflux through trafficking APP to the cell surface in normal physiology. Tau hyperphosphorylation and aggregation impair surface trafficking of APP, thereby contributing to toxic neuronal iron accumulation and aggravating NFTs, which leads to a vicious cycle. Indeed, the tau-mediated APP pathway can prevent ferroptotic damage by reducing iron-mediated neurotoxicity in a transient middle cerebral artery occlusion (MCAO) rat model. Therefore, iron- and tau-mediated generation of ROS is an important mechanism of neuron damage and death.

Ferroptosis Linking With AD

Aging is one of the greatest risk factors for the disease. And iron accumulates in the brain with aging processes; brain iron deposition is more serious in special regions in neurodegenerative diseases associated with oxidative stress and neuronal death. Indeed, brain iron dysregulation along with reduced endogenous antioxidant systems including GPX is closely linked to AD pathology. The level of brain iron is positively correlated with AD progression and cognitive decline. Patients with mild cognitive impairment accompanying high Aβ plaque load showed higher cortical iron, which increased the risk of AD.

The brain is more susceptible to oxidative damage than other tissues owing to high demand for dynamic energy metabolism. And neurons are less tolerant of oxidative stress due to a low antioxidant defense system. The progressive loss of neurons is a direct cause of clinical symptoms correlating with AD. And oxidative stress is an essential pathological mechanism of AD. Iron is an essential cofactor for metabolic reactions, but iron also can generate ROS and causes oxidative stress in the same microenvironment. Indeed, iron-induced oxidative stress directly causes destructive DNA, lipid, and protein damage, thereby leading to cell death. Recent studies also found that iron plays a key role in ferroptosis, a newly defined non-apoptotic cell death. Lipid peroxidation and iron dyshomeostasis and accumulation, two essential conditions of ferroptosis, have long been noted in AD brains. That ferroptosis may contribute to the neuronal loss of AD attracts more and more attention. Ferroptosis, a novel form of cell death characterized by intracellular iron overload, may provide us a new perspective to understand the pathological mechanism of AD.

Glutathione peroxidase 4 is a unique anti-peroxidant enzyme, which inhibits lipid peroxidation through directly reducing membrane lipid hydroperoxides to lipid alcohols. And GPX4 is considered as the central regulator of ferroptosis. Indeed, multiple studies showed that lipid peroxidation and depletion or reduction of GSH levels, the other signature of ferroptosis, also occur in AD. Recent studies revealed that hippocampi’s and frontal cortices’ GSH levels have the potential to be a predictive biomarker for AD and MCI. The research shows that ablation of GPX4 induces ferroptosis of spinal motor neurons, thereby resulting in rapid onset and progression of paralysis and death in adult mice. Further research shows that ferroptosis triggers the major cell death in hippocampal neurodegeneration by ablation of forebrain neuron GPX4, which directly relates to cognitive impairment. And the hallmarks of ferroptosis (iron dysregulation, lipid peroxidation, inflammation) are recognized as important preclinical signs of AD and cognitive impairment. In addition, research shows that α-lipoic acid (LA) administration could block tau-induced iron overload, lipid peroxidation, and inflammation, which are involved in ferroptosis. Iron interacts with Aβ and tau through the deposition of iron and the formation of a peptide–hemin complex, thereby participating in generating ROS that possibly involves the ferroptotic death pathway. Taken together, although ferroptosis in AD is unproven, it is gradually attracting more and more attention.

Conclusion

Alzheimer’s disease is characterized by progressive cortical and hippocampal neuronal dysfunction and death; the major hypothesis mechanisms are Aβ depositions in SPs and NFTs of hyperphosphorylated tau protein. However, a large number of drug clinical trials based on these two hypotheses worldwide have failed; there is still no effective way to treat it. Furthermore, the two hypotheses are subject to a growing challenge. Indeed, it has been widely accepted that iron participates in the pathogenesis of AD. Iron not only aggravates toxic Aβ and hyperphosphorylated tau aggregation but also directly induces neuronal oxidative damage. Considering the particularity and importance of iron in ferroptosis and the pathomechanism of AD, ferroptosis may provide a new insight into the molecular pathophysiology of the disease. Thus, future research aimed at validating the role of ferroptosis in AD is needed.

Author Contributions

NY drafted the manuscript. JZ revised the manuscript. Both authors read and approved the final manuscript.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References 138

  1. 1.
    Targeting Nrf2 to Suppress Ferroptosis and Mitochondrial Dysfunction in Neurodegeneration · 2018
    No notice
  2. 2.

    Alim I. Caulfield J. T. Chen Y. Swarup V. Geschwind D. H. Ivanova E. (2019 ). Selenium drives a transcriptional adaptive program to block ferroptosis and treat stroke. Cell 177 1262–1279.e25.

    Not in our library10.1016/j.cell.2019.03.032

  3. 3.

    Altamura S. Muckenthaler M. U. (2009 ). Iron toxicity in diseases of aging: Alzheimer’s disease, Parkinson’s disease and atherosclerosis. J. Alzheimers Dis. 16 879–895.

    Not in our library10.3233/jad-2009-1010

  4. 4.

    Angeli J. P. F. Shah R. Pratt D. A. Conrad M. (2017 ). Ferroptosis inhibition: mechanisms and opportunities. Trends Pharmacol. Sci. 38 489–498.

    Not in our library10.1016/j.tips.2017.02.005

  5. 5.

    Apostolakis S. Kypraiou A. M. (2017 ). Iron in neurodegenerative disorders: being in the wrong place at the wrong time? Rev. Neurosci. 28 893–911.

    Not in our library10.1515/revneuro-2017-0020

  6. 6.

    Aron A. T. Loehr M. O. Bogena J. Chang C. J. (2016 ). An endoperoxide reactivity-based FRET probe for ratiometric fluorescence imaging of labile iron pools in living cells. J. Am. Chem. Soc. 138 14338–14346.

    Not in our library10.1021/jacs.6b08016

  7. 7.

    Ayton S. Diouf I. Bush A. I. (2018 ). Evidence that iron accelerates Alzheimer’s pathology: a CSF biomarker study. J. Neurol. Neurosurg. Psychiatry 89 456–460.

    Not in our library10.1136/jnnp-2017-316551

  8. 8.
    Ferritin levels in the cerebrospinal fluid predict Alzheimer’s disease outcomes and are regulated by APOE · 2015
    No notice
  9. 9.

    Ayton S. Faux N. G. Bush A. I. (2017a ). Association of cerebrospinal fluid ferritin level with preclinical cognitive decline in APOE-epsilon4 carriers. JAMA Neurol. 74 122–125.

    Not in our library10.1001/jamaneurol.2016.4406

  10. 10.

    Ayton S. Fazlollahi A. Bourgeat P. Raniga P. Ng A. Lim Y. Y. (2017b ). Cerebral quantitative susceptibility mapping predicts amyloid-beta-related cognitive decline. Brain 140 2112–2119.

    Not in our library10.1093/brain/awx137

  11. 11.

    Ayton S. Wang Y. Diouf I. Schneider J. A. Brockman J. Morris M. C. (2019 ). Brain iron is associated with accelerated cognitive decline in people with Alzheimer pathology. Mol. Psychiatry [Epub ahead of print].

    Not in our library10.1038/s41380-019-0375-7

  12. 12.

    Becerril-Ortega J. Bordji K. Freret T. Rush T. Buisson A. (2014 ). Iron overload accelerates neuronal amyloid-beta production and cognitive impairment in transgenic mice model of Alzheimer’s disease. Neurobiol. Aging 35 2288–2301.

    Not in our library10.1016/j.neurobiolaging.2014.04.019

  13. 13.

    Belaidi A. A. Bush A. I. (2016 ). Iron neurochemistry in Alzheimer’s disease and Parkinson’s disease: targets for therapeutics. J. Neurochem. 139(Suppl. 1), 179–197.

    Not in our library10.1111/jnc.13425

  14. 14.

    Belaidi A. A. Gunn A. P. Wong B. X. Ayton S. Appukuttan A. T. Roberts B. R. (2018 ). Marked age-related changes in brain iron homeostasis in amyloid protein precursor knockout mice. Neurotherapeutics 15 1055–1062.

    Not in our library10.1007/s13311-018-0656-x

  15. 15.

    Biasiotto G. Di Lorenzo D. Archetti S. Zanella I. (2016 ). Iron and neurodegeneration: is ferritinophagy the link? Mol. Neurobiol. 53 5542–5574.

    Not in our library10.1007/s12035-015-9473-y

  16. 16.

    Bogdan A. R. Miyazawa M. Hashimoto K. Tsuji Y. (2016 ). Regulators of iron homeostasis: new players in metabolism, cell death, and disease. Trends Biochem. Sci. 41 274–286.

    Not in our library10.1016/j.tibs.2015.11.012

  17. 17.

    Bu X. L. Xiang Y. Guo Y. (2019 ). The role of iron in amyotrophic lateral sclerosis. Adv. Exp. Med. Biol. 1173 145–152.

    Not in our library10.1007/978-981-13-9589-5_8

  18. 18.

    Bulk M. Abdelmoula W. M. Nabuurs R. J. A. van der Graaf L. M. Mulders C. W. H. Mulder A. A. (2018 ). Postmortem MRI and histology demonstrate differential iron accumulation and cortical myelin organization in early- and late-onset Alzheimer’s disease. Neurobiol. Aging 62 231–242.

    Not in our library10.1016/j.neurobiolaging.2017.10.017

  19. 19.
    Mechanisms of ferroptosis · 2016
    No notice
  20. 20.

    Chen L. Hambright W. S. Na R. Ran Q. (2015 ). Ablation of the ferroptosis inhibitor glutathione peroxidase 4 in neurons results in rapid motor neuron degeneration and paralysis. J. Biol. Chem. 290 28097–28106.

    Not in our library10.1074/jbc.m115.680090

  21. 21.

    Chiou B. Lucassen E. Sather M. Kallianpur A. Connor J. (2018 ). Semaphorin4A and H-ferritin utilize Tim-1 on human oligodendrocytes: a novel neuro-immune axis. Glia 66 1317–1330.

    Not in our library10.1002/glia.23313

  22. 22.

    Chiou B. Neal E. H. Bowman A. B. Lippmann E. S. Simpson I. A. Connor J. R. (2019a ). Endothelial cells are critical regulators of iron transport in a model of the human blood-brain barrier. J. Cereb. Blood Flow Metab. 39 2117–2131.

    Not in our library10.1177/0271678x18783372

  23. 23.

    Chiou B. Neely E. B. McDevitt D. S. Simpson I. A. Connor J. R. (2019b ). Transferrin and H-ferritin involvement in brain iron acquisition during postnatal development: impact of sex and genotype. J. Neurochem. [Epub ahead of print].

    Not in our library10.1111/jnc.14834

  24. 24.

    Cobley J. N. Fiorello M. L. Bailey D. M. (2018 ). 13 reasons why the brain is susceptible to oxidative stress. Redox Biol. 15 490–503.

    Not in our library10.1016/j.redox.2018.01.008

  25. 25.
    New insights into the role of iron in inflammation and atherosclerosis · 2019
    Not checked
  26. 26.

    Cozza G. Rossetto M. Bosello-Travain V. Maiorino M. Roveri A. Toppo S. (2017 ). Glutathione peroxidase 4-catalyzed reduction of lipid hydroperoxides in membranes: the polar head of membrane phospholipids binds the enzyme and addresses the fatty acid hydroperoxide group toward the redox center. Free Radic. Biol. Med. 112 1–11.

    Not in our library10.1016/j.freeradbiomed.2017.07.010

  27. 27.

    Daneman R. Prat A. (2015 ). The blood-brain barrier. Cold Spring Harb. Perspect. Biol. 7:a020412.

    Not in our library10.1101/cshperspect.a020412

  28. 28.

    Derry P. J. Hegde M. L. Jackson G. R. Kayed R. Tour J. M. Tsai A. L. (2019 ). Revisiting the intersection of amyloid, pathologically modified Tau and iron in Alzheimer’s disease from a ferroptosis perspective. Prog. Neurobiol. 184:101716.

    Not in our library10.1016/j.pneurobio.2019.101716

  29. 29.

    Derry P. J. Kent T. A. (2017 ). Correlating quantitative susceptibility mapping with cognitive decline in Alzheimer’s disease. Brain 140 2069–2072.

    Not in our library10.1093/brain/awx167

  30. 30.

    Dev S. Babitt J. L. (2017 ). Overview of iron metabolism in health and disease. Hemodial. Int. 21(Suppl. 1), S6–S20.

    Not in our library10.1111/hdi.12542

  31. 31.

    Diouf I. Fazlollahi A. Bush A. I. Ayton S. (2019 ). Cerebrospinal fluid ferritin levels predict brain hypometabolism in people with underlying beta-amyloid pathology. Neurobiol. Dis. 124 335–339.

    Not in our library10.1016/j.nbd.2018.12.010

  32. 32.

    Dixon S. J. Lemberg K. M. Lamprecht M. R. Skouta R. Zaitsev E. M. Gleason C. E. (2012 ). Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149 1060–1072.

    Not in our library10.1016/j.cell.2012.03.042

  33. 33.

    Dixon S. J. Stockwell B. R. (2013 ). The role of iron and reactive oxygen species in cell death. Nat. Chem. Biol. 10 9–17.

    Not in our library10.1038/nchembio.1416

  34. 34.

    Doll S. Conrad M. (2017 ). Iron and ferroptosis: a still ill-defined liaison. IUBMB Life 69 423–434.

    Not in our library10.1002/iub.1616

  35. 35.

    Dolma S. Lessnick S. L. Hahn W. C. Stockwell B. R. (2003 ). Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell 3 285–296.

    Not in our library10.1016/s1535-6108(03)00050-3

  36. 36.

    Dowdle W. E. Nyfeler B. Nagel J. Elling R. A. Liu S. Triantafellow E. (2014 ). Selective VPS34 inhibitor blocks autophagy and uncovers a role for NCOA4 in ferritin degradation and iron homeostasis in vivo. Nat. Cell Biol. 16 1069–1079.

    Not in our library10.1038/ncb3053

  37. 37.

    Drecourt A. Babdor J. Dussiot M. Petit F. Goudin N. Garfa-Traoré M. (2018 ). Impaired transferrin receptor palmitoylation and recycling in neurodegeneration with brain iron accumulation. Am. J. Hum. Genet. 102 266–277.

    Not in our library10.1016/j.ajhg.2018.01.003

  38. 38.

    Dringen R. (2000 ). Metabolism and functions of glutathione in brain. Prog. Neurobiol. 62 649–671.

    Not in our library10.1016/s0301-0082(99)00060-x

  39. 39.

    Du L. Zhao Z. Cui A. Zhu Y. Zhang L. Liu J. (2018 ). Increased iron deposition on brain quantitative susceptibility mapping correlates with decreased cognitive function in Alzheimer’s disease. ACS Chem. Neurosci. 9 1849–1857.

    Not in our library10.1021/acschemneuro.8b00194

  40. 40.

    Duck K. A. Simpson I. A. Connor J. R. (2017 ). Regulatory mechanisms for iron transport across the blood-brain barrier. Biochem. Biophys. Res. Commun. 494 70–75.

    Not in our library10.1016/j.bbrc.2017.10.083

  41. 41.

    Dugger B. N. Dickson D. W. (2017 ). Pathology of neurodegenerative diseases. Cold Spring Harbor. Perspect. Biol. 9:a028035.

    Not in our library10.1101/cshperspect.a028035

  42. 42.

    Everett J. Collingwood J. F. Tjendana-Tjhin V. Brooks J. Lermyte F. Plascencia-Villa G. (2018 ). Nanoscale synchrotron X-ray speciation of iron and calcium compounds in amyloid plaque cores from Alzheimer’s disease subjects. Nanoscale 10 11782–11796.

    Not in our library10.1039/c7nr06794a

  43. 43.

    Fanzani A. Poli M. (2017 ). Iron, oxidative damage and ferroptosis in rhabdomyosarcoma. Int. J. Mol. Sci. 18:E1718.

    Not in our library10.3390/ijms18081718

  44. 44.

    Friedmann Angeli J. P. Schneider M. Proneth B. Tyurina Y. Y. Tyurin V. A. Hammond V. J. (2014 ). Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat. Cell Biol. 16 1180–1191.

    Not in our library10.1038/ncb3064

  45. 45.

    Ganz T. (2013 ). Systemic iron homeostasis. Physiol. Rev. 93 1721–1741.

    Not in our library10.1152/physrev.00008.2013

  46. 46.

    Gao M. Monian P. Pan Q. Zhang W. Xiang J. Jiang X. (2016 ). Ferroptosis is an autophagic cell death process. Cell Res. 26 1021–1032.

    Not in our library10.1038/cr.2016.95

  47. 47.

    Gao M. Monian P. Quadri N. Ramasamy R. Jiang X. (2015 ). Glutaminolysis and transferrin regulate ferroptosis. Mol. Cell 59 298–308.

    Not in our library10.1016/j.molcel.2015.06.011

  48. 48.
    Iron Dyshomeostasis Induces Binding of APP to BACE1 for Amyloid Pathology, and Impairs APP/Fpn1 Complex in Microglia: Implication in Pathogenesis of Cerebral Microbleeds · 2019
    Not checked
  49. 49.

    Guillemot J. Canuel M. Essalmani R. Prat A. Seidah N. G. (2013 ). Implication of the proprotein convertases in iron homeostasis: proprotein convertase 7 sheds human transferrin receptor 1 and furin activates hepcidin. Hepatology 57 2514–2524.

    Not in our library10.1002/hep.26297

  50. 50.

    Guo C. Wang P. Zhong M. L. Wang T. Huang X. S. Li J. Y. (2013 ). Deferoxamine inhibits iron induced hippocampal Tau phosphorylation in the Alzheimer transgenic mouse brain. Neurochem. Int. 62 165–172.

    Not in our library10.1016/j.neuint.2012.12.005

  51. 51.

    Hambright W. S. Fonseca R. S. Chen L. Na R. Ran Q. (2017 ). Ablation of ferroptosis regulator glutathione peroxidase 4 in forebrain neurons promotes cognitive impairment and neurodegeneration. Redox Biol. 12 8–17.

    Not in our library10.1016/j.redox.2017.01.021

  52. 52.
    A delicate balance: Iron metabolism and diseases of the brain · 2013
    No notice
  53. 53.

    Hirschhorn T. Stockwell B. R. (2019 ). The development of the concept of ferroptosis. Free Radic. Biol. Med. 133 130–143.

    Not in our library10.1016/j.freeradbiomed.2018.09.043

  54. 54.

    Hou W. Xie Y. Song X. Sun X. Lotze M. T. Zeh H. J. (2016 ). Autophagy promotes ferroptosis by degradation of ferritin. Autophagy 12 1425–1428.

    Not in our library10.1080/15548627.2016.1187366

  55. 55.

    Imai H. Matsuoka M. Kumagai T. Sakamoto T. Koumura T. (2017 ). Lipid peroxidation-dependent cell death regulated by GPx4 and ferroptosis. Curr. Top. Microbiol. Immunol. 403 143–170.

    Not in our library10.1007/82_2016_508

  56. 56.

    Ingrassia R. Garavaglia B. Memo M. (2019 ). DMT1 expression and iron levels at the crossroads between aging and neurodegeneration. Front. Neurosci. 13:575.

    Not in our library10.3389/fnins.2019.00575

  57. 57.

    Joppe K. Roser A.-E. Maass F. Lingor P. (2019 ). The contribution of iron to protein aggregation disorders in the central nervous system. Front. Neurosci. 13:15.

    Not in our library10.3389/fnins.2019.00015

  58. 58.

    Jouanne M. Rault S. Voisin-Chiret A. S. (2017 ). Tau protein aggregation in Alzheimer’s disease: an attractive target for the development of novel therapeutic agents. Eur. J. Med. Chem. 139 153–167.

    Not in our library10.1016/j.ejmech.2017.07.070

  59. 59.

    Kagan V. E. Mao G. Qu F. Angeli J. P. Doll S. Croix C. S. (2017 ). Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. Nat. Chem. Biol. 13 81–90.

    Not in our library10.1038/nchembio.2238

  60. 60.

    Ke Y. Ming Qian Z. (2003 ). Iron misregulation in the brain: a primary cause of neurodegenerative disorders. Lancet Neurol. 2 246–253.

    Not in our library10.1016/s1474-4422(03)00353-3

  61. 61.

    Kenkhuis B. Jonkman L. E. Bulk M. Buijs M. Boon B. D. C. Bouwman F. H. (2019 ). 7T MRI allows detection of disturbed cortical lamination of the medial temporal lobe in patients with Alzheimer’s disease. Neuroimage Clin. 21:101665.

    Not in our library10.1016/j.nicl.2019.101665

  62. 62.

    Kenny E. M. Fidan E. Yang Q. Anthonymuthu T. S. New L. A. Meyer E. A. (2019 ). Ferroptosis contributes to neuronal death and functional outcome after traumatic brain injury. Crit. Care Med. 47 410–418.

    Not in our library10.1097/ccm.0000000000003555

  63. 63.
    Metal Ion Effects on Aβ and Tau Aggregation · 2018
    No notice
  64. 64.

    Kroner A. Greenhalgh A. D. Zarruk J. G. Passos Dos Santos R. Gaestel M. David S. (2014 ). TNF and increased intracellular iron alter macrophage polarization to a detrimental M1 phenotype in the injured spinal cord. Neuron 83 1098–1116.

    Not in our library10.1016/j.neuron.2014.07.027

  65. 65.

    Lal A. (2019 ). Iron in health and disease: an update. Indian J. Pediatr. 87 58–65.

    Not in our library10.1007/s12098-019-03054-8

  66. 66.

    Lane C. A. Hardy J. Schott J. M. (2018 ). Alzheimer’s disease. Eur. J. Neurol. 25 59–70.

    Not in our library10.1111/ene.13439

  67. 67.
    Brain Iron Accumulation in Atypical Parkinsonian Syndromes: in vivo MRI Evidences for Distinctive Patterns · 2019
    Not checked
  68. 68.

    Lei P. Ayton S. Finkelstein D. I. Spoerri L. Ciccotosto G. D. Wright D. K. (2012 ). Tau deficiency induces Parkinsonism with dementia by impairing APP-mediated iron export. Nat. Med. 18 291–295.

    Not in our library10.1038/nm.2613

  69. 69.

    Leong Y. Q. Ng K. Y. Chye S. M. Ling A. P. K. Koh R. Y. (2019 ). Mechanisms of action of amyloid-beta and its precursor protein in neuronal cell death. Metab. Brain Dis. [Epub ahead of print].

    Not in our library10.1007/s11011-019-00516-y

  70. 70.

    Levi S. Taveggia C. (2014 ). Iron homeostasis in peripheral nervous system, still a black box? Antioxid. Redox Signal. 21 634–648.

    Not in our library10.1089/ars.2013.5813

  71. 71.

    Li Y. Zhou Y. Zhang D. Wu W. Y. Kang X. Wu Q. (2019 ). Hypobaric hypoxia regulates iron metabolism in rats. J. Cell. Biochem. 120 14076–14087.

    Not in our library10.1002/jcb.28683

  72. 72.
    Iron and Alzheimer’s Disease: From Pathogenesis to Therapeutic Implications · 2018
    No notice
  73. 73.

    Liu Y. Nguyen M. Robert A. Meunier B. (2019 ). Metal ions in Alzheimer’s disease: a key role or not? Acc. Chem. Res. 52 2026–2035.

    Not in our library10.1021/acs.accounts.9b00248

  74. 74.

    Lupton M. K. Benyamin B. Proitsi P. Nyholt D. R. Ferreira M. A. Montgomery G. W. (2017 ). No genetic overlap between circulating iron levels and Alzheimer’s disease. J. Alzheimers Dis. 59 85–99.

    Not in our library10.3233/jad-170027

  75. 75.

    Mancias J. D. Wang X. Gygi S. P. Harper J. W. Kimmelman A. C. (2014 ). Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. Nature 509 105–109.

    Not in our library10.1038/nature13148

  76. 76.

    Mandal P. K. Saharan S. Tripathi M. Murari G. (2015 ). Brain glutathione levels–a novel biomarker for mild cognitive impairment and Alzheimer’s disease. Biol. Psychiatry 78 702–710.

    Not in our library10.1016/j.biopsych.2015.04.005

  77. 77.

    Masaldan S. Bush A. I. Devos D. Rolland A. S. Moreau C. (2019 ). Striking while the iron is hot: iron metabolism and ferroptosis in neurodegeneration. Free Radic. Biol. Med. 133 221–233.

    Not in our library10.1016/j.freeradbiomed.2018.09.033

  78. 78.

    McCarthy R. C. Kosman D. J. (2015 ). Iron transport across the blood-brain barrier: development, neurovascular regulation and cerebral amyloid angiopathy. Cell. Mol. Life Sci. 72 709–727.

    Not in our library10.1007/s00018-014-1771-4

  79. 79.

    McIntosh A. Mela V. Harty C. Minogue A. M. Costello D. A. Kerskens C. (2019 ). Iron accumulation in microglia triggers a cascade of events that leads to altered metabolism and compromised function in APP/PS1 mice. Brain Pathol. 29 606–621.

    Not in our library10.1111/bpa.12704

  80. 80.

    Mills E. Dong X.-P. Wang F. Xu H. (2010 ). Mechanisms of brain iron transport: insight into neurodegeneration and CNS disorders. Future Med. Chem. 2 51–64.

    Not in our library10.4155/fmc.09.140

  81. 81.

    Morris G. Berk M. Carvalho A. F. Maes M. Walker A. J. Puri B. K. (2018 ). Why should neuroscientists worry about iron? The emerging role of ferroptosis in the pathophysiology of neuroprogressive diseases. Behav. Brain Res. 341 154–175.

    Not in our library10.1016/j.bbr.2017.12.036

  82. 82.
    Ferroptosis, a new form of cell death: opportunities and challenges in cancer · 2019
    No notice
  83. 83.
    Iron in Neurodegeneration – Cause or Consequence? · 2019
    No notice
  84. 84.

    Nikseresht S. Bush A. I. Ayton S. (2019 ). Treating Alzheimer’s disease by targeting iron. Br. J. Pharmacol. 176 3622–3635.

    Not in our library10.1111/bph.14567

  85. 85.

    Pantopoulos K. Porwal S. K. Tartakoff A. Devireddy L. (2012 ). Mechanisms of mammalian iron homeostasis. Biochemistry 51 5705–5724.

    Not in our library10.1021/bi300752r

  86. 86.
    ROS-mediated autophagy increases intracellular iron levels and ferroptosis by ferritin and transferrin receptor regulation · 2019
    No notice
  87. 87.

    Patel M. Ramavataram D. V. (2012 ). Non transferrin bound iron: nature, manifestations and analytical approaches for estimation. Indian J. Clin. Biochem. 27 322–332.

    Not in our library10.1007/s12291-012-0250-7

  88. 88.

    Peters D. G. Connor J. R. Meadowcroft M. D. (2015 ). The relationship between iron dyshomeostasis and amyloidogenesis in Alzheimer’s disease: two sides of the same coin. Neurobiol. Dis. 81 49–65.

    Not in our library10.1016/j.nbd.2015.08.007

  89. 89.

    Qian Z. M. Ke Y. (2019 ). Brain iron transport. Biol. Rev. 94 1672–1684.

    Not in our library10.1111/brv.12521

  90. 90.
    NCOA4-Mediated Ferritinophagy: A Potential Link to Neurodegeneration · 2019
    No notice
  91. 91.

    Rao S. S. Adlard P. A. (2018 ). Untangling Tau and iron: exploring the interaction between iron and Tau in neurodegeneration. Front. Mol. Neurosci. 11:276.

    Not in our library10.3389/fnmol.2018.00276

  92. 92.

    Rogers J. T. Bush A. I. Cho H. H. Smith D. H. Thomson A. M. Friedlich A. L. (2008 ). Iron and the translation of the amyloid precursor protein (APP) and ferritin mRNAs: riboregulation against neural oxidative damage in Alzheimer’s disease. Biochem. Soc. Trans. 36(Pt 6), 1282–1287.

    Not in our library10.1042/bst0361282

  93. 93.

    Roubroeks J. A. Y. Smith R. G. van den Hove D. L. A. Lunnon K. (2017 ). Epigenetics and DNA methylomic profiling in Alzheimer’s disease and other neurodegenerative diseases. J. Neurochem. 143 158–170.

    Not in our library10.1111/jnc.14148

  94. 94.

    Salazar J. Mena N. Hunot S. Prigent A. Alvarez-Fischer D. Arredondo M. (2008 ). Divalent metal transporter 1 (DMT1) contributes to neurodegeneration in animal models of Parkinson’s disease. Proc. Natl. Acad. Sci. U.S.A. 105 18578–18583.

    Not in our library10.1073/pnas.0804373105

  95. 95.

    Sangkhae V. Nemeth E. (2017 ). Regulation of the iron homeostatic hormone hepcidin. Adv. Nutr. 8 126–136.

    Not in our library10.3945/an.116.013961

  96. 96.

    Sayre L. M. Perry G. Harris P. L. Liu Y. Schubert K. A. Smith M. A. (2000 ). In situ oxidative catalysis by neurofibrillary tangles and senile plaques in Alzheimer’s disease: a central role for bound transition metals. J. Neurochem. 74 270–279.

    Not in our library10.1046/j.1471-4159.2000.0740270.x

  97. 97.

    Shintoku R. Takigawa Y. Yamada K. Kubota C. Yoshimoto Y. Takeuchi T. (2017 ). Lipoxygenase-mediated generation of lipid peroxides enhances ferroptosis induced by erastin and RSL3. Cancer Sci. 108 2187–2194.

    Not in our library10.1111/cas.13380

  98. 98.

    Simpson I. A. Ponnuru P. Klinger M. E. Myers R. L. Devraj K. Coe C. L. (2015 ). A novel model for brain iron uptake: introducing the concept of regulation. J. Cereb. Blood Flow Metab. 35 48–57.

    Not in our library10.1038/jcbfm.2014.168

  99. 99.

    Skjorringe T. Moller L. B. Moos T. (2012 ). Impairment of interrelated iron- and copper homeostatic mechanisms in brain contributes to the pathogenesis of neurodegenerative disorders. Front. Pharmacol. 3:169.

    Not in our library10.3389/fphar.2012.00169

  100. 100.

    Stockwell B. R. Friedmann Angeli J. P. Bayir H. Bush A. I. Conrad M. Dixon S. J. (2017 ). Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell 171 273–285.

    Not in our library10.1016/j.cell.2017.09.021

  101. 101.

    Stoyanovsky D. A. Tyurina Y. Y. Shrivastava I. Bahar I. Tyurin V. A. Protchenko O. (2019 ). Iron catalysis of lipid peroxidation in ferroptosis: regulated enzymatic or random free radical reaction? Free Radic. Biol. Med. 133 153–161.

    Not in our library10.1016/j.freeradbiomed.2018.09.008

  102. 102.

    Tang M. Chen Z. Wu D. Chen L. (2018 ). Ferritinophagy/ferroptosis: iron-related newcomers in human diseases. J. Cell. Physiol. 233 9179–9190.

    Not in our library10.1002/jcp.26954

  103. 103.

    Telling N. D. Everett J. Collingwood J. F. Dobson J. van der Laan G. Gallagher J. J. (2017 ). Iron biochemistry is correlated with amyloid plaque morphology in an established mouse model of Alzheimer’s disease. Cell Chem. Biol. 24 1205–1215.e3.

    Not in our library10.1016/j.chembiol.2017.07.014

  104. 104.

    Thapa A. Carroll N. J. (2017 ). Dietary modulation of oxidative stress in Alzheimer’s disease. Int. J. Mol. Sci. 18:E1583.

    Not in our library10.3390/ijms18071583

  105. 105.

    Theil E. C. (2013 ). Ferritin: the protein nanocage and iron biomineral in health and in disease. Inorg. Chem. 52 12223–12233.

    Not in our library10.1021/ic400484n

  106. 106.

    Thirupathi A. Chang Y. Z. (2019 ). Brain iron metabolism and CNS diseases. Adv. Exp. Med. Biol. 1173 1–19.

    Not in our library10.1007/978-981-13-9589-5_1

  107. 107.

    Todorich B. Zhang X. Connor J. R. (2011 ). H-ferritin is the major source of iron for oligodendrocytes. Glia 59 927–935.

    Not in our library10.1002/glia.21164

  108. 108.

    Tsatsanis A. Dickens S. Kwok J. C. F. Wong B. X. Duce J. A. (2019 ). Post translational modulation of β-amyloid precursor protein trafficking to the cell surface alters neuronal iron homeostasis. Neurochem. Res. 44 1367–1374.

    Not in our library10.1007/s11064-019-02747-y

  109. 109.

    Tuo Q. Z. Lei P. Jackman K. A. Li X. L. Xiong H. Li X. L. (2017 ). Tau-mediated iron export prevents ferroptotic damage after ischemic stroke. Mol. Psychiatry 22 1520–1530.

    Not in our library10.1038/mp.2017.171

  110. 110.

    Uranga R. M. Salvador G. A. (2018 ). Unraveling the burden of iron in neurodegeneration: intersections with amyloid beta peptide pathology. Oxid. Med. Cell. Longev. 2018:2850341.

    Not in our library10.1155/2018/2850341

  111. 111.

    Urrutia P. Aguirre P. Esparza A. Tapia V. Mena N. P. Arredondo M. (2013 ). Inflammation alters the expression of DMT1, FPN1 and hepcidin, and it causes iron accumulation in central nervous system cells. J. Neurochem. 126 541–549.

    Not in our library10.1111/jnc.12244

  112. 112.
    Colocalization of cerebral iron with Amyloid beta in Mild Cognitive Impairment · 2016
    No notice
  113. 113.

    van Bergen J. M. G. Li X. Quevenco F. C. Gietl A. F. Treyer V. Meyer R. (2018 ). Simultaneous quantitative susceptibility mapping and flutemetamol-PET suggests local correlation of iron and β-amyloid as an indicator of cognitive performance at high age. Neuroimage 174 308–316.

    Not in our library10.1016/j.neuroimage.2018.03.021

  114. 114.

    van Duijn S. Bulk M. van Duinen S. G. Nabuurs R. J. A. van Buchem M. A. van der Weerd L. (2017 ). Cortical iron reflects severity of Alzheimer’s disease. J. Alzheimers Dis. 60 1533–1545.

    Not in our library10.3233/jad-161143

  115. 115.

    Vanden Berghe T. Linkermann A. Jouan-Lanhouet S. Walczak H. Vandenabeele P. (2014 ). Regulated necrosis: the expanding network of non-apoptotic cell death pathways. Nat. Rev. Mol. Cell Biol. 15 135–147.

    Not in our library10.1038/nrm3737

  116. 116.

    Vossel K. A. Xu J. C. Fomenko V. Miyamoto T. Suberbielle E. Knox J. A. (2015 ). Tau reduction prevents Abeta-induced axonal transport deficits by blocking activation of GSK3beta. J. Cell Biol. 209 419–433.

    Not in our library10.1083/jcb.201407065

  117. 117.

    Wan W. Cao L. Kalionis B. Murthi P. Xia S. Guan Y. (2019 ). Iron deposition leads to hyperphosphorylation of Tau and disruption of insulin signaling. Front. Neurol. 10:607.

    Not in our library10.3389/fneur.2019.00607

  118. 118.

    Wang C. Y. Babitt J. L. (2019 ). Liver iron sensing and body iron homeostasis. Blood 133 18–29.

    Not in our library10.1182/blood-2018-06-815894

  119. 119.

    Wang T. Xu S. F. Fan Y. G. Li L. B. Guo C. (2019 ). Iron pathophysiology in Alzheimer’s diseases. Adv. Exp. Med. Biol. 1173 67–104.

    Not in our library10.1007/978-981-13-9589-5_5

  120. 120.
    Modifications and Trafficking of APP in the Pathogenesis of Alzheimer’s Disease · 2017
    No notice
  121. 121.

    Wang Y. Mandelkow E. (2016 ). Tau in physiology and pathology. Nat. Rev. Neurosci. 17 22–35.

    Not in our library10.1038/nrn.2015.1

  122. 122.

    Ward R. J. Zucca F. A. Duyn J. H. Crichton R. R. Zecca L. (2014 ). The role of iron in brain ageing and neurodegenerative disorders. Lancet Neurol. 13 1045–1060.

    Not in our library10.1016/s1474-4422(14)70117-6

  123. 123.

    Weiland A. Wang Y. Wu W. Lan X. Han X. Li Q. (2018 ). Ferroptosis and its role in diverse brain diseases. Mol. Neurobiol. 56 4880–4893.

    Not in our library10.1007/s12035-018-1403-3

  124. 124.

    Weinreb O. Amit T. Bar-Am O. Youdim M. B. H. (2016 ). Neuroprotective effects of multifaceted hybrid agents targeting MAO, cholinesterase, iron and β-amyloid in ageing and Alzheimer’s disease. Br. J. Pharmacol. 173 2080–2094.

    Not in our library10.1111/bph.13318

  125. 125.

    Wojtunik-Kulesza K. Oniszczuk A. Waksmundzka-Hajnos M. (2019 ). An attempt to elucidate the role of iron and zinc ions in development of Alzheimer’s and Parkinson’s diseases. Biomed. Pharmacother. 111 1277–1289.

    Not in our library10.1016/j.biopha.2018.12.140

  126. 126.
    β-Amyloid Precursor Protein Does Not Possess Ferroxidase Activity but Does Stabilize the Cell Surface Ferrous Iron Exporter Ferroportin · 2014
    No notice
  127. 127.

    Xie Y. Hou W. Song X. Yu Y. Huang J. Sun X. (2016 ). Ferroptosis: process and function. Cell Death Differ. 23 369–379.

    Not in our library10.1038/cdd.2015.158

  128. 128.

    Xu M. Tan X. Li N. Wu H. Wang Y. Xie J. (2019 ). Differential regulation of estrogen in iron metabolism in astrocytes and neurons. J. Cell. Physiol. 234 4232–4242.

    Not in our library10.1002/jcp.27188

  129. 129.

    Xu S. (2019 ). Iron and atherosclerosis: the link revisited. Trends Mol. Med. 25 659–661.

    Not in our library10.1016/j.molmed.2019.05.012

  130. 130.

    Yan N. Zhang J.-J. (2019 ). The emerging roles of ferroptosis in vascular cognitive impairment. Front. Neurosci. 13:811.

    Not in our library10.3389/fnins.2019.00811

  131. 131.

    Yang W. S. Stockwell B. R. (2008 ). Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. Chem. Biol. 15 234–245.

    Not in our library10.1016/j.chembiol.2008.02.010

  132. 132.

    Yang W. S. Stockwell B. R. (2016 ). Ferroptosis: death by lipid peroxidation. Trends Cell Biol. 26 165–176.

    Not in our library10.1016/j.tcb.2015.10.014

  133. 133.
    A Short Review of Iron Metabolism and Pathophysiology of Iron Disorders · 2019
    No notice
  134. 134.

    Yu P. Chang Y. Z. (2019 ). Brain iron metabolism and regulation. Adv. Exp. Med. Biol. 1173 33–44.

    Not in our library10.1007/978-981-13-9589-5_3

  135. 135.

    Zarruk J. G. Berard J. L. Passos dos Santos R. Kroner A. Lee J. Arosio P. (2015 ). Expression of iron homeostasis proteins in the spinal cord in experimental autoimmune encephalomyelitis and their implications for iron accumulation. Neurobiol. Dis. 81 93–107.

    Not in our library10.1016/j.nbd.2015.02.001

  136. 136.

    Zhang C.-W. Tai Y. K. Chai B.-H. Chew K. C. M. Ang E.-T. Tsang F. (2017 ). Transgenic mice overexpressing the divalent metal transporter 1 exhibit iron accumulation and enhanced Parkin expression in the brain. Neuromol. Med. 19 375–386.

    Not in our library10.1007/s12017-017-8451-0

  137. 137.

    Zhang Y. H. Wang D. W. Xu S. F. Zhang S. Fan Y. G. Yang Y. Y. (2018 ). alpha-lipoic acid improves abnormal behavior by mitigation of oxidative stress, inflammation, ferroptosis, and tauopathy in P301S Tau transgenic mice. Redox Biol. 14 535–548.

    Not in our library10.1016/j.redox.2017.11.001

  138. 138.

    Zhou B. Liu J. Kang R. Klionsky D. J. Kroemer G. Tang D. (2019 ). Ferroptosis is a type of autophagy-dependent cell death. Semin. Cancer Biol. [Epub ahead of print].

    Not in our library10.1016/j.semcancer.2019.03.002

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