Skip to content
2000
Volume 31, Issue 10
  • ISSN: 0929-8665
  • E-ISSN: 1875-5305

Abstract

Amidst the rising global burden of neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, there is an urgent need for novel therapeutic strategies to combat these debilitating conditions. These diseases are characterized by progressive neural dysfunction leading to cognitive impairments, for which current therapeutic strategies remain palliative at best. Recently, the discovery of ferroptosis, a novel cell death mode that is different from apoptosis and autophagy, has opened new avenues in the field of cognitive research. With in-depth research on ferroptosis, the clinical significance of iron homeostasis disorders and lipid peroxidation in the occurrence, development, and treatment of neurodegenerative diseases are gradually becoming apparent. This study aims to elucidate the roles of ferroptosis in the context of neurodegeneration and to explore its potential as a therapeutic target. By unraveling the intricate relationship between iron homeostasis disorders, oxidative damage, and lipid metabolism disturbances in these diseases, new intervention targets are revealed. It offers a new dimension to the management of neurocognitive impairments in Alzheimer's and Parkinson's diseases. The implications of these findings extend beyond just Alzheimer's and Parkinson's diseases. They also have relevance with other neurological conditions characterized by oxidative stress and iron dysregulation. This review contributes to increased knowledge of ferroptosis and provides a foundational understanding that could lead to the development of innovative therapeutic strategies. Ultimately, it may alleviate the development of neurodegenerative diseases and improve cognitive function by preventing ferroptosis, which has not only academic significance but also potential clinical significance.

Loading

Article metrics loading...

/content/journals/ppl/10.2174/0109298665333926240927074528
2024-11-07
2025-01-19
Loading full text...

Full text loading...

References

  1. DixonS.J. LembergK.M. LamprechtM.R. SkoutaR. ZaitsevE.M. GleasonC.E. PatelD.N. BauerA.J. CantleyA.M. YangW.S. MorrisonB.III StockwellB.R. Ferroptosis: An iron-dependent form of nonapoptotic cell death.Cell201214951060107210.1016/j.cell.2012.03.04222632970
    [Google Scholar]
  2. CerasuoloM. Di MeoI. AuriemmaM.C. TrojsiF. MaiorinoM.I. CirilloM. EspositoF. PolitoR. ColangeloA.M. PaolissoG. PapaM. RizzoM.R. Iron and ferroptosis more than a suspect: Beyond the most common mechanisms of neurodegeneration for new therapeutic approaches to cognitive decline and dementia.Int. J. Mol. Sci.20232411963710.3390/ijms2411963737298586
    [Google Scholar]
  3. YanH. ZouT. TuoQ. XuS. LiH. BelaidiA.A. LeiP. Ferroptosis: Mechanisms and links with diseases.Signal Transduct. Target. Ther.2021614910.1038/s41392‑020‑00428‑933536413
    [Google Scholar]
  4. SinghN. HaldarS. TripathiA.K. HorbackK. WongJ. SharmaD. BeserraA. SudaS. AnbalaganC. DevS. MukhopadhyayC.K. SinghA. Brain iron homeostasis: From molecular mechanisms to clinical significance and therapeutic opportunities.Antioxid. Redox Signal.20142081324136310.1089/ars.2012.493123815406
    [Google Scholar]
  5. CrichtonR.R. DexterD.T. WardR.J. Brain iron metabolism and its perturbation in neurological diseases.J. Neural Transm. (Vienna)2011118330131410.1007/s00702‑010‑0470‑z20809066
    [Google Scholar]
  6. OnukwuforJ.O. DirksenR.T. WojtovichA.P. Iron dysregulation in mitochondrial dysfunction and Alzheimer’s disease.Antioxidants202211469210.3390/antiox1104069235453377
    [Google Scholar]
  7. ZhouJ. JinY. LeiY. LiuT. WanZ. MengH. WangH. Ferroptosis is regulated by mitochondria in neurodegenerative diseases.Neurodegener. Dis.2020201203410.1159/00051008332814328
    [Google Scholar]
  8. RogersJ.T. CahillC.M. Iron-responsive-like elements and neurodegenerative ferroptosis.Learn. Mem.202027939541310.1101/lm.052282.12032817306
    [Google Scholar]
  9. WonJ.P. KimE. HurJ. LeeH.G. LeeW.J. SeoH.G. Red clover (Trifolium pratense L.) extract inhibits ferroptotic cell death by modulating cellular iron homeostasis.J. Ethnopharmacol.202330811626710.1016/j.jep.2023.11626736796742
    [Google Scholar]
  10. DetmerS.A. ChanD.C. Functions and dysfunctions of mitochondrial dynamics.Nat. Rev. Mol. Cell Biol.200781187087910.1038/nrm227517928812
    [Google Scholar]
  11. YangW.S. StockwellB.R. Ferroptosis: Death by lipid peroxidation.Trends Cell Biol.201626316517610.1016/j.tcb.2015.10.01426653790
    [Google Scholar]
  12. ButterfieldD.A. LauderbackC.M. Lipid peroxidation and protein oxidation in Alzheimer’s disease brain: potential causes and consequences involving amyloid β-peptide-associated free radical oxidative stress.Free Radic. Biol. Med.200232111050106010.1016/S0891‑5849(02)00794‑312031889
    [Google Scholar]
  13. ChanD.C. Mitochondrial fusion and fission in mammals.Annu. Rev. Cell Dev. Biol.2006221799910.1146/annurev.cellbio.22.010305.10463816704336
    [Google Scholar]
  14. ParkJ. LeeD.G. KimB. ParkS.J. KimJ.H. LeeS.R. ChangK.T. LeeH.S. LeeD.S. Iron overload triggers mitochondrial fragmentation via calcineurin-sensitive signals in HT-22 hippocampal neuron cells.Toxicology2015337394610.1016/j.tox.2015.08.00926318285
    [Google Scholar]
  15. HuangX.T. LiuX. YeC.Y. TaoL.X. ZhouH. ZhangH.Y. Iron-induced energy supply deficiency and mitochondrial fragmentation in neurons.J. Neurochem.2018147681683010.1111/jnc.1462130380148
    [Google Scholar]
  16. XieY. HouW. SongX. YuY. HuangJ. SunX. KangR. TangD. Ferroptosis: Process and function.Cell Death Differ.201623336937910.1038/cdd.2015.15826794443
    [Google Scholar]
  17. WangY.Q. ChangS.Y. WuQ. GouY.J. JiaL. CuiY.M. YuP. ShiZ.H. WuW.S. GaoG. ChangY.Z. The protective role of mitochondrial ferritin on erastin-induced ferroptosis.Front. Aging Neurosci.2016830810.3389/fnagi.2016.0030828066232
    [Google Scholar]
  18. YuanH. LiX. ZhangX. KangR. TangD. CISD1 inhibits ferroptosis by protection against mitochondrial lipid peroxidation.Biochem. Biophys. Res. Commun.2016478283884410.1016/j.bbrc.2016.08.03427510639
    [Google Scholar]
  19. StoyanovskyD.A. TyurinaY.Y. ShrivastavaI. BaharI. TyurinV.A. ProtchenkoO. JadhavS. BolevichS.B. KozlovA.V. VladimirovY.A. ShvedovaA.A. PhilpottC.C. BayirH. KaganV.E. Iron catalysis of lipid peroxidation in ferroptosis: Regulated enzymatic or random free radical reaction?Free Radic. Biol. Med.201913315316110.1016/j.freeradbiomed.2018.09.00830217775
    [Google Scholar]
  20. QuX. LiangT. WuD. LaiN. DengR. MaC. LiX. LiH. LiuY. ShenH. ChenG. Acyl-CoA synthetase long chain family member 4 plays detrimental role in early brain injury after subarachnoid hemorrhage in rats by inducing ferroptosis.CNS Neurosci. Ther.202127444946310.1111/cns.1354833314758
    [Google Scholar]
  21. ChaseL.A. VerHeulen KleynM. SchillerN. KingA.G. FloresG. EngelsmanS.B. BowlesC. SmithS.L. RobinsonA.E. RothsteinJ. Hydrogen peroxide triggers an increase in cell surface expression of system xc − in cultured human glioma cells.Neurochem. Int.202013410464810.1016/j.neuint.2019.10464831874187
    [Google Scholar]
  22. BersukerK. HendricksJ.M. LiZ. MagtanongL. FordB. TangP.H. RobertsM.A. TongB. MaimoneT.J. ZoncuR. BassikM.C. NomuraD.K. DixonS.J. OlzmannJ.A. The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis.Nature2019575778468869210.1038/s41586‑019‑1705‑231634900
    [Google Scholar]
  23. DollS. FreitasF.P. ShahR. AldrovandiM. da SilvaM.C. IngoldI. Goya GrocinA. Xavier da SilvaT.N. PanziliusE. ScheelC.H. MourãoA. BudayK. SatoM. WanningerJ. VignaneT. MohanaV. RehbergM. FlatleyA. SchepersA. KurzA. WhiteD. SauerM. SattlerM. TateE.W. SchmitzW. SchulzeA. O’DonnellV. PronethB. PopowiczG.M. PrattD.A. AngeliJ.P.F. ConradM. FSP1 is a glutathione-independent ferroptosis suppressor.Nature2019575778469369810.1038/s41586‑019‑1707‑031634899
    [Google Scholar]
  24. LiY. ZhaoY. LiX. ZhaiL. ZhengH. YanY. FuQ. MaJ. FuH. ZhangZ. LiZ. Biological and therapeutic role of LSD1 in alzheimer’s diseases.Front. Pharmacol.202213102055610.3389/fphar.2022.102055636386192
    [Google Scholar]
  25. AytonS. WangY. DioufI. SchneiderJ.A. BrockmanJ. MorrisM.C. BushA.I. Brain iron is associated with accelerated cognitive decline in people with alzheimer pathology.Mol. Psychiatry202025112932294110.1038/s41380‑019‑0375‑730778133
    [Google Scholar]
  26. LvJ. XuS. MengC. WangY. JiL. LiX. WangX. LiQ. Ferroptosis participated in hippocampal neuroinflammation damage of in offspring rats after maternal sleep deprivation.J. Neuroimmunol.202337557802110.1016/j.jneuroim.2023.57802136681050
    [Google Scholar]
  27. WangC. ChenS. GuoH. JiangH. LiuH. FuH. WangD. Forsythoside a mitigates alzheimer’s-like pathology by inhibiting ferroptosis-mediated neuroinflammation via Nrf2/GPX4 axis activation.Int. J. Biol. Sci.20221852075209010.7150/ijbs.6971435342364
    [Google Scholar]
  28. DeTureM.A. DicksonD.W. The neuropathological diagnosis of alzheimer’s disease.Mol. Neurodegener.20191413210.1186/s13024‑019‑0333‑531375134
    [Google Scholar]
  29. GleasonA. BushA.I. Iron and ferroptosis as therapeutic targets in alzheimer’s disease.Neurotherapeutics202118125226410.1007/s13311‑020‑00954‑y33111259
    [Google Scholar]
  30. MasaldanS. BelaidiA.A. AytonS. BushA.I. Cellular senescence and iron dyshomeostasis in alzheimer’s disease.Pharmaceuticals (Basel)20191229310.3390/ph1202009331248150
    [Google Scholar]
  31. EverettJ. CéspedesE. ShelfordL.R. ExleyC. CollingwoodJ.F. DobsonJ. van der LaanG. JenkinsC.A. ArenholzE. TellingN.D. Ferrous iron formation following the co-aggregation of ferric iron and the alzheimer’s disease peptide β-amyloid (1–42).J. R. Soc. Interface201411952014016510.1098/rsif.2014.016524671940
    [Google Scholar]
  32. BaoW.D. PangP. ZhouX.T. HuF. XiongW. ChenK. WangJ. WangF. XieD. HuY.Z. HanZ.T. ZhangH.H. WangW.X. NelsonP.T. ChenJ.G. LuY. ManH.Y. LiuD. ZhuL.Q. Loss of ferroportin induces memory impairment by promoting ferroptosis in alzheimer’s disease.Cell Death Differ.20212851548156210.1038/s41418‑020‑00685‑933398092
    [Google Scholar]
  33. ChoH.H. CahillC.M. VanderburgC.R. ScherzerC.R. WangB. HuangX. RogersJ.T. Selective translational control of the Alzheimer amyloid precursor protein transcript by iron regulatory protein-1.J. Biol. Chem.201028541312173123210.1074/jbc.M110.14916120558735
    [Google Scholar]
  34. AytonS. PortburyS. KalinowskiP. AgarwalP. DioufI. SchneiderJ.A. MorrisM.C. BushA.I. Regional brain iron associated with deterioration in alzheimer’s disease: A large cohort study and theoretical significance.Alzheimers Dement.20211771244125610.1002/alz.1228233491917
    [Google Scholar]
  35. ChenL. DarN.J. NaR. McLaneK.D. YooK. HanX. RanQ. Enhanced defense against ferroptosis ameliorates cognitive impairment and reduces neurodegeneration in 5xFAD mice.Free Radic. Biol. Med.202218011210.1016/j.freeradbiomed.2022.01.00234998934
    [Google Scholar]
  36. HambrightW.S. FonsecaR.S. ChenL. NaR. RanQ. Ablation of ferroptosis regulator glutathione peroxidase 4 in forebrain neurons promotes cognitive impairment and neurodegeneration.Redox Biol.20171281710.1016/j.redox.2017.01.02128212525
    [Google Scholar]
  37. YangJ.H. NguyenC.D. LeeG. NaC.S. Insamgobonhwan protects neuronal cells from lipid ros and improves deficient cognitive function.Antioxidants202211229510.3390/antiox1102029535204177
    [Google Scholar]
  38. AtesG. GoldbergJ. CurraisA. MaherP. CMS121, a fatty acid synthase inhibitor, protects against excess lipid peroxidation and inflammation and alleviates cognitive loss in a transgenic mouse model of alzheimer’s disease.Redox Biol.20203610164810.1016/j.redox.2020.10164832863221
    [Google Scholar]
  39. BelaidiA.A. MasaldanS. SouthonA. KalinowskiP. AcevedoK. AppukuttanA.T. PortburyS. LeiP. AgarwalP. LeurgansS.E. SchneiderJ. ConradM. BushA.I. AytonS. Apolipoprotein E potently inhibits ferroptosis by blocking ferritinophagy.Mol. Psychiatry20222922112010.1038/s41380‑022‑01568‑w35484240
    [Google Scholar]
  40. DangY. HeQ. YangS. SunH. LiuY. LiW. TangY. ZhengY. WuT. FTH1- and SAT1-induced astrocytic ferroptosis is involved in alzheimer’s disease: Evidence from single-cell transcriptomic analysis.Pharmaceuticals (Basel)20221510117710.3390/ph1510117736297287
    [Google Scholar]
  41. YiS. WangL. WangH. HoM.S. ZhangS. Pathogenesis of α-synuclein in parkinson’s disease: From a neuron-glia crosstalk perspective.Int. J. Mol. Sci.202223231475310.3390/ijms23231475336499080
    [Google Scholar]
  42. AytonS. LeiP. McleanC. BushA.I. FinkelsteinD.I. Transferrin protects against parkinsonian neurotoxicity and is deficient in parkinson’s substantia nigra.Signal Transduct. Target. Ther.2016111601510.1038/sigtrans.2016.1529263898
    [Google Scholar]
  43. Sian-HulsmannJ. RiedererP. The role of alpha-synuclein as ferrireductase in neurodegeneration associated with parkinson’s disease.J. Neural Transm. (Vienna)2020127574975410.1007/s00702‑020‑02192‑032318880
    [Google Scholar]
  44. AytonS. LeiP. DuceJ.A. WongB.X.W. SedjahteraA. AdlardP.A. BushA.I. FinkelsteinD.I. Ceruloplasmin dysfunction and therapeutic potential for parkinson disease.Ann. Neurol.201373455455910.1002/ana.2381723424051
    [Google Scholar]
  45. AnH. ZengX. NiuT. LiG. YangJ. ZhengL. ZhouW. LiuH. ZhangM. HuangD. LiJ. Quantifying iron deposition within the substantia nigra of parkinson’s disease by quantitative susceptibility mapping.J. Neurol. Sci.2018386465210.1016/j.jns.2018.01.00829406966
    [Google Scholar]
  46. HouL. SunF. SunW. ZhangL. WangQ. Lesion of the locus coeruleus damages learning and memory performance in paraquat and maneb-induced mouse parkinson’s disease model.Neuroscience201941912914010.1016/j.neuroscience.2019.09.00631634513
    [Google Scholar]
  47. DevosD. MoreauC. DevedjianJ.C. KluzaJ. PetraultM. LalouxC. JonneauxA. RyckewaertG. GarçonG. RouaixN. DuhamelA. JissendiP. DujardinK. AugerF. RavasiL. HopesL. GrolezG. FirdausW. SablonnièreB. Strubi-VuillaumeI. ZahrN. DestéeA. CorvolJ.C. PöltlD. LeistM. RoseC. DefebvreL. MarchettiP. CabantchikZ.I. BordetR. Targeting chelatable iron as a therapeutic modality in parkinson’s disease.Antioxid. Redox Signal.201421219521010.1089/ars.2013.559324251381
    [Google Scholar]
  48. WangD. ZhangS. GeX. YinZ. LiM. GuoM. HuT. HanZ. KongX. LiD. ZhaoJ. WangL. LiuQ. ChenF. LeiP. Mesenchymal stromal cell treatment attenuates repetitive mild traumatic brain injury-induced persistent cognitive deficits via suppressing ferroptosis.J. Neuroinflammation202219118510.1186/s12974‑022‑02550‑735836233
    [Google Scholar]
  49. XieB.S. WangY.Q. LinY. MaoQ. FengJ.F. GaoG.Y. JiangJ.Y. Inhibition of ferroptosis attenuates tissue damage and improves long-term outcomes after traumatic brain injury in mice.CNS Neurosci. Ther.201925446547510.1111/cns.1306930264934
    [Google Scholar]
  50. BaoZ. LiuY. ChenB. MiaoZ. TuY. LiC. ChaoH. YeY. XuX. SunG. ZhaoP. LiuN. LiuY. WangX. LamS.M. KaganV.E. BayırH. JiJ. Prokineticin-2 prevents neuronal cell deaths in a model of traumatic brain injury.Nat. Commun.2021121422010.1038/s41467‑021‑24469‑y34244497
    [Google Scholar]
  51. WehnA.C. KhalinI. DueringM. HellalF. CulmseeC. VandenabeeleP. PlesnilaN. TerpolilliN.A. RIPK1 or RIPK3 deletion prevents progressive neuronal cell death and improves memory function after traumatic brain injury.Acta Neuropathol. Commun.20219113810.1186/s40478‑021‑01236‑034404478
    [Google Scholar]
  52. LiC. WuZ. XueH. GaoQ. ZhangY. WangC. ZhaoP. Ferroptosis contributes to hypoxic–ischemic brain injury in neonatal rats: Role of the SIRT1 /Nrf2/ GPx4 signaling pathway.CNS Neurosci. Ther.202228122268228010.1111/cns.1397336184790
    [Google Scholar]
  53. ChenK.N. GuanQ.W. YinX.X. WangZ.J. ZhouH.H. MaoX.Y. Ferrostatin-1 obviates seizures and associated cognitive deficits in ferric chloride-induced posttraumatic epilepsy via suppressing ferroptosis.Free Radic. Biol. Med.202217910911810.1016/j.freeradbiomed.2021.12.26834952157
    [Google Scholar]
  54. XuP. KongL. TaoC. ZhuY. ChengJ. LiW. ShenN. LiR. ZhangC. WangL. ZhangY. WangG. LiuX. SunW. HuW. Elabela-APJ axis attenuates cerebral ischemia/reperfusion injury by inhibiting neuronal ferroptosis.Free Radic. Biol. Med.202319617118610.1016/j.freeradbiomed.2023.01.00836681202
    [Google Scholar]
  55. ChenW. JiangL. HuY. TangN. LiangN. LiX.F. ChenY.W. QinH. WuL. Ferritin reduction is essential for cerebral ischemia-induced hippocampal neuronal death through p53/SLC7A11-mediated ferroptosis.Brain Res.2021175214721610.1016/j.brainres.2020.14721633333054
    [Google Scholar]
  56. AnJ.R. SuJ.N. SunG.Y. WangQ.F. FanY.D. JiangN. YangY.F. ShiY. Liraglutide alleviates cognitive deficit in db/db mice: Involvement in oxidative stress, iron overload, and ferroptosis.Neurochem. Res.202247227929410.1007/s11064‑021‑03442‑734480710
    [Google Scholar]
  57. XieZ. WangX. LuoX. YanJ. ZhangJ. SunR. LuoA. LiS. Activated AMPK mitigates diabetes-related cognitive dysfunction by inhibiting hippocampal ferroptosis.Biochem. Pharmacol.202320711537410.1016/j.bcp.2022.11537436502872
    [Google Scholar]
  58. HaoL. MiJ. SongL. GuoY. LiY. YinY. ZhangC. SLC40A1 mediates ferroptosis and cognitive dysfunction in type 1 diabetes.Neuroscience202146321622610.1016/j.neuroscience.2021.03.00933727075
    [Google Scholar]
  59. AbdulY. LiW. WardR. AbdelsaidM. HafezS. DongG. JamilS. WolfV. JohnsonM.H. FaganS.C. ErgulA. Deferoxamine treatment prevents post-stroke vasoregression and neurovascular unit remodeling leading to improved functional outcomes in type 2 male diabetic rats: role of endothelial ferroptosis.Transl. Stroke Res.202112461563010.1007/s12975‑020‑00844‑732875455
    [Google Scholar]
  60. LiW. AbdulY. ChandranR. JamilS. WardR.A. AbdelsaidM. DongG. FaganS.C. ErgulA. Deferoxamine prevents poststroke memory impairment in female diabetic rats: potential links to hemorrhagic transformation and ferroptosis.Am. J. Physiol. Heart Circ. Physiol.20233242H212H22510.1152/ajpheart.00490.202236563009
    [Google Scholar]
  61. WangJ. YangS. JingG. WangQ. ZengC. SongX. LiX. Inhibition of ferroptosis protects sepsis-associated encephalopathy.Cytokine202316115607810.1016/j.cyto.2022.15607836401983
    [Google Scholar]
  62. ChuJ. JiangY. ZhouW. ZhangJ. LiH. YuY. YuY. Acetaminophen alleviates ferroptosis in mice with sepsis-associated encephalopathy via the GPX4 pathway.Hum. Exp. Toxicol.202241p. 0960327122113354710.1177/0960327122113354736214461
    [Google Scholar]
  63. DangR. WangM. LiX. WangH. LiuL. WuQ. ZhaoJ. JiP. ZhongL. LicinioJ. XieP. Edaravone ameliorates depressive and anxiety-like behaviors via Sirt1/Nrf2/HO-1/Gpx4 pathway.J. Neuroinflammation20221914110.1186/s12974‑022‑02400‑635130906
    [Google Scholar]
  64. LiuZ. HuangY. WangX. HeY. LiJ. LiB. The role of ferroptosis in chronic intermittent hypoxia-induced cognitive impairment.Sleep Breath.20232751725173210.1007/s11325‑022‑02760‑636607542
    [Google Scholar]
  65. XieR. ZhaoW. LoweS. BentleyR. HuG. MeiH. JiangX. SunC. WuY. Yueying liu Quercetin alleviates kainic acid-induced seizure by inhibiting the Nrf2-mediated ferroptosis pathway.Free Radic. Biol. Med.202219121222610.1016/j.freeradbiomed.2022.09.00136087883
    [Google Scholar]
  66. LiY. ZhangE. YangH. ChenY. TaoL. XuY. ChenT. ShenX. Gastrodin ameliorates cognitive dysfunction in vascular dementia rats by suppressing ferroptosis via the regulation of the Nrf2/Keap1-GPx4 signaling pathway.Molecules20222719631110.3390/molecules2719631136234847
    [Google Scholar]
  67. ChangC.F. ChoS. WangJ. (-)-Epicatechin protects hemorrhagic brain via synergistic Nrf2 pathways.Ann. Clin. Transl. Neurol.20141425827110.1002/acn3.5424741667
    [Google Scholar]
  68. HouW. XieY. SongX. SunX. LotzeM.T. ZehH.J.III KangR. TangD. Autophagy promotes ferroptosis by degradation of ferritin.Autophagy20161281425142810.1080/15548627.2016.118736627245739
    [Google Scholar]
  69. SongX. ZhuS. ChenP. HouW. WenQ. LiuJ. XieY. LiuJ. KlionskyD.J. KroemerG. LotzeM.T. ZehH.J. KangR. TangD. AMPK-Mediated BECN1 phosphorylation promotes ferroptosis by directly blocking system Xc – Activity.Curr. Biol.2018281523882399.e510.1016/j.cub.2018.05.09430057310
    [Google Scholar]
  70. TangM. ChenZ. WuD. ChenL. Ferritinophagy/ferroptosis: Iron-related newcomers in human diseases.J. Cell. Physiol.2018233129179919010.1002/jcp.2695430076709
    [Google Scholar]
  71. XuR. WangW. ZhangW. Ferroptosis and the bidirectional regulatory factor p53.Cell Death Discov.20239119710.1038/s41420‑023‑01517‑837386007
    [Google Scholar]
  72. KistM. VucicD. Cell death pathways: intricate connections and disease implications.EMBO J.2021405e10670010.15252/embj.202010670033439509
    [Google Scholar]
  73. ZilleM. KaruppagounderS.S. ChenY. GoughP.J. BertinJ. FingerJ. MilnerT.A. JonasE.A. RatanR.R. Neuronal death after hemorrhagic stroke in vitro and in vivo shares features of ferroptosis and necroptosis.Stroke20174841033104310.1161/STROKEAHA.116.01560928250197
    [Google Scholar]
  74. KitamuraY. ShimohamaS. KamoshimaW. OtaT. MatsuokaY. NomuraY. SmithM.A. PerryG. WhitehouseP.J. TaniguchiT. Alteration of proteins regulating apoptosis, Bcl-2, Bcl-x, Bax, Bak, Bad, ICH-1 and CPP32, in Alzheimer’s disease.Brain Res.1998780226026910.1016/S0006‑8993(97)01202‑X9507158
    [Google Scholar]
  75. OhyagiY. AsaharaH. ChuiD.H. TsurutaY. SakaeN. MiyoshiK. YamadaT. KikuchiH. TaniwakiT. MuraiH. IkezoeK. FuruyaH. KawarabayashiT. ShojiM. CheclerF. IwakiT. MakifuchiT. TakedaK. KiraJ.I. TabiraT. Intracellular Aβ42 activates p53 promoter: A pathway to neurodegeneration in alzheimer’s disease.FASEB J.200519212910.1096/fj.04‑2637fje15548589
    [Google Scholar]
  76. ZhangY. McLaughlinR. GoodyerC. LeBlancA. Selective cytotoxicity of intracellular amyloid β peptide1–42 through p53 and Bax in cultured primary human neurons.J. Cell Biol.2002156351952910.1083/jcb.20011011911815632
    [Google Scholar]
  77. ParkG. NhanH.S. TyanS.H. KawakatsuY. ZhangC. NavarroM. KooE.H. Caspase activation and caspase-mediated cleavage of APP is associated with amyloid β-protein-induced synapse loss in alzheimer’s disease.Cell Rep.2020311310783910.1016/j.celrep.2020.10783932610140
    [Google Scholar]
  78. YangS.H. LeeD.K. ShinJ. LeeS. BaekS. KimJ. JungH. HahJ.M. KimY. Nec-1 alleviates cognitive impairment with reduction of Aβ and tau abnormalities in APP / PS 1 mice.EMBO Mol. Med.201791617710.15252/emmm.20160656627861127
    [Google Scholar]
  79. OfengeimD. MazzitelliS. ItoY. DeWittJ.P. MifflinL. ZouC. DasS. AdiconisX. ChenH. ZhuH. KelliherM.A. LevinJ.Z. YuanJ. RIPK1 mediates a disease-associated microglial response in alzheimer’s disease.Proc. Natl. Acad. Sci. USA201711441E8788E879710.1073/pnas.171417511428904096
    [Google Scholar]
  80. BolandB. KumarA. LeeS. PlattF.M. WegielJ. YuW.H. NixonR.A. Autophagy induction and autophagosome clearance in neurons: Relationship to autophagic pathology in alzheimer’s disease.J. Neurosci.200828276926693710.1523/JNEUROSCI.0800‑08.200818596167
    [Google Scholar]
  81. OñateM. CatenaccioA. SalvadoresN. SaquelC. MartinezA. Moreno-GonzalezI. GamezN. SotoP. SotoC. HetzC. CourtF.A. Correction: The necroptosis machinery mediates axonal degeneration in a model of parkinson disease.Cell Death Differ.2020277229410.1038/s41418‑020‑0507‑232047275
    [Google Scholar]
  82. IannielliA. BidoS. FolladoriL. SegnaliA. CancellieriC. MarescaA. MassiminoL. RubioA. MorabitoG. CaporaliL. TagliaviniF. MusumeciO. GregatoG. BezardE. CarelliV. TirantiV. BroccoliV. Pharmacological inhibition of necroptosis protects from dopaminergic neuronal cell death in parkinson’s disease models.Cell Rep.20182282066207910.1016/j.celrep.2018.01.08929466734
    [Google Scholar]
  83. BlandiniF. MangiagalliA. CosentinoM. MarinoF. SamueleA. RasiniE. FancelluR. MartignoniE. RiboldazziG. CalandrellaD. FrigoG.M. NappiG. Peripheral markers of apoptosis in parkinson’s disease: The effect of dopaminergic drugs.Ann. N. Y. Acad. Sci.20031010167567810.1196/annals.1299.12315033810
    [Google Scholar]
  84. TattonN.A. Increased caspase 3 and Bax immunoreactivity accompany nuclear GAPDH translocation and neuronal apoptosis in Parkinson’s disease.Exp. Neurol.20001661294310.1006/exnr.2000.748911031081
    [Google Scholar]
  85. FriedmanL.G. LachenmayerM.L. WangJ. HeL. PouloseS.M. KomatsuM. HolsteinG.R. YueZ. Disrupted autophagy leads to dopaminergic axon and dendrite degeneration and promotes presynaptic accumulation of α-synuclein and LRRK2 in the brain.J. Neurosci.201232227585759310.1523/JNEUROSCI.5809‑11.201222649237
    [Google Scholar]
  86. LiL. LiW.J. ZhengX.R. LiuQ.L. DuQ. LaiY.J. LiuS.Q. Eriodictyol ameliorates cognitive dysfunction in APP/PS1 mice by inhibiting ferroptosis via vitamin D receptor-mediated Nrf2 activation.Mol. Med.20222811110.1186/s10020‑022‑00442‑335093024
    [Google Scholar]
  87. MaZ. MaY. CaoX. ZhangY. SongT. Avenanthramide-C activates nrf2/are pathway and inhibiting ferroptosis pathway to improve cognitive dysfunction in aging rats.Neurochem. Res.202348239340310.1007/s11064‑022‑03754‑236222956
    [Google Scholar]
  88. CaiW. YangT. LiuH. HanL. ZhangK. HuX. ZhangX. YinK.J. GaoY. BennettM.V.L. LeakR.K. ChenJ. Peroxisome proliferator-activated receptor γ (PPARγ): A master gatekeeper in CNS injury and repair.Prog. Neurobiol.2018163-164275810.1016/j.pneurobio.2017.10.00229032144
    [Google Scholar]
  89. ZhangY. LanJ. ZhaoD. RuanC. ZhouJ. TanH. BaoY. Netrin-1 upregulates GPX4 and prevents ferroptosis after traumatic brain injury via the UNC5B/Nrf2 signaling pathway.CNS Neurosci. Ther.202329121622710.1111/cns.1399736468399
    [Google Scholar]
  90. FuC. WuY. LiuS. LuoC. LuY. LiuM. WangL. ZhangY. LiuX. Rehmannioside A improves cognitive impairment and alleviates ferroptosis via activating PI3K/AKT/Nrf2 and SLC7A11/GPX4 signaling pathway after ischemia.J. Ethnopharmacol.202228911502110.1016/j.jep.2022.11502135091012
    [Google Scholar]
  91. YangY. WangX. XiaoA. HanJ. WangZ. WenM. Ketogenic diet prevents chronic sleep deprivation-induced Alzheimer’s disease by inhibiting iron dyshomeostasis and promoting repair via Sirt1/Nrf2 pathway.Front. Aging Neurosci.20221499829210.3389/fnagi.2022.99829236118706
    [Google Scholar]
  92. ChengL. ZhuX. LiuY. ZhuK. LinK. LiF. ACSL4 contributes to sevoflurane-induced ferroptotic neuronal death in SH-SY5Y cells via the 5′ AMP-activated protein kinase/ mammalian target of rapamycin pathway.Ann. Transl. Med.2021918145410.21037/atm‑21‑424934734006
    [Google Scholar]
  93. LiJ. LiM. GeY. ChenJ. MaJ. WangC. SunM. WangL. YaoS. YaoC. β-amyloid protein induces mitophagy-dependent ferroptosis through the cd36/pink/parkin pathway leading to blood–brain barrier destruction in alzheimer’s disease.Cell Biosci.20221216910.1186/s13578‑022‑00807‑535619150
    [Google Scholar]
  94. ZhaoY. ZhangJ. ZhangY. LiS. GaoY. ChangC. LiuX. XuL. YangG. Proteomic Analysis of Protective Effects of Dl-3-n-Butylphthalide against mpp+ -Induced Toxicity via downregulating P53 pathway in N2A Cells.Proteome Sci.2023211110.1186/s12953‑022‑00199‑x36597095
    [Google Scholar]
  95. YangS. WangL. ZengY. WangY. PeiT. XieZ. XiongQ. WeiH. LiW. LiJ. SuQ. WeiD. ChengW. Salidroside alleviates cognitive impairment by inhibiting ferroptosis via activation of the Nrf2/GPX4 axis in SAMP8 mice.Phytomedicine202311415476210.1016/j.phymed.2023.15476236965372
    [Google Scholar]
  96. ShaoL. DongC. GengD. HeQ. ShiY. Ginkgolide B protects against cognitive impairment in senescence-accelerated P8 mice by mitigating oxidative stress, inflammation and ferroptosis.Biochem. Biophys. Res. Commun.202157271410.1016/j.bbrc.2021.07.08134332327
    [Google Scholar]
  97. LinZ.H. LiuY. XueN.J. ZhengR. YanY.Q. WangZ.X. LiY.L. YingC.Z. SongZ. TianJ. PuJ.L. ZhangB.R. Quercetin protects against MPP+/MPTP-induced dopaminergic neuron death in parkinson’s disease by inhibiting ferroptosis.Oxid. Med. Cell. Longev.2022202211710.1155/2022/776935536105483
    [Google Scholar]
  98. XiJ. ZhangZ. WangZ. WuQ. HeY. XuY. DingZ. ZhaoH. DaH. ZhangF. ZhaoH. FangJ. Hinokitiol functions as a ferroptosis inhibitor to confer neuroprotection.Free Radic. Biol. Med.202219020221510.1016/j.freeradbiomed.2022.08.01135985562
    [Google Scholar]
  99. WangL. AnH. YuF. YangJ. DingH. BaoY. XieH. HuangD. The neuroprotective effects of paeoniflorin against MPP+-induced damage to dopaminergic neurons via the Akt/Nrf2/GPX4 pathway.J. Chem. Neuroanat.202212210210310.1016/j.jchemneu.2022.10210335489613
    [Google Scholar]
  100. ZengX. AnH. YuF. WangK. ZhengL. ZhouW. BaoY. YangJ. ShenN. HuangD. Benefits of iron chelators in the treatment of parkinson’s disease.Neurochem. Res.20214651239125110.1007/s11064‑021‑03262‑933646533
    [Google Scholar]
  101. AvcıB. GünaydınC. GüvençT. YavuzC.K. KurucaN. BilgeS.S. Idebenone ameliorates rotenone-induced parkinson’s disease in rats through decreasing lipid peroxidation.Neurochem. Res.202146351352210.1007/s11064‑020‑03186‑w33247801
    [Google Scholar]
  102. YuX. YangY. ZhangB. HanG. YuJ. YuQ. ZhangL. Ketone body β-hydroxybutyric acid ameliorates dopaminergic neuron injury through modulating zinc finger protein 36/acyl-coa synthetase long-chain family member four signaling axis-mediated ferroptosis.Neuroscience202350915717210.1016/j.neuroscience.2022.11.01836435477
    [Google Scholar]
  103. LiK. WangM. HuangZ.H. WangM. SunW.Y. KuriharaH. HuangR.T. WangR. HuangF. LiangL. LiY.F. DuanW.J. HeR.R. ALOX5 inhibition protects against dopaminergic neurons undergoing ferroptosis.Pharmacol. Res.202319310677910.1016/j.phrs.2023.10677937121496
    [Google Scholar]
  104. LiuH. ZhaoZ. YanM. ZhangQ. JiangT. XueJ. Calycosin decreases cerebral ischemia/reperfusion injury by suppressing ACSL4-dependent ferroptosis.Arch. Biochem. Biophys.202373410948810.1016/j.abb.2022.10948836516890
    [Google Scholar]
  105. TangJ.J. HuangL.F. DengJ.L. WangY.M. GuoC. PengX.N. LiuZ. GaoJ.M. Cognitive enhancement and neuroprotective effects of oabl, a sesquiterpene lactone in 5xfad alzheimer’s disease mice model.Redox Biol.20225010222910.1016/j.redox.2022.10222935026701
    [Google Scholar]
  106. YanN. XuZ. QuC. ZhangJ. Dimethyl fumarate improves cognitive deficits in chronic cerebral hypoperfusion rats by alleviating inflammation, oxidative stress, and ferroptosis via NRF2/ARE/NF-κB signal pathway.Int. Immunopharmacol.20219810784410.1016/j.intimp.2021.10784434153667
    [Google Scholar]
  107. LiuY. ChenZ. LiB. YaoH. ZarkaM. WelchJ. SachdevP. BridgeW. BraidyN. Supplementation with γ-glutamylcysteine (γ-GC) lessens oxidative stress, brain inflammation and amyloid pathology and improves spatial memory in a murine model of AD.Neurochem. Int.202114410493110.1016/j.neuint.2020.10493133276023
    [Google Scholar]
  108. QuX.X. HeJ.H. CuiZ.Q. YangT. SunX.H. PPAR-α agonist GW7647 protects against oxidative stress and iron deposit via gpx4 in a transgenic mouse model of alzheimer’s diseases.ACS Chem. Neurosci.202213220721610.1021/acschemneuro.1c0051634965724
    [Google Scholar]
  109. ShenL-H. LuoQ-Q. HuC-B. JiangH. YangY. WangG-H. JiQ-H. JiaZ-Z. DL-3-n-butylphthalide alleviates motor disturbance by suppressing ferroptosis in a rat model of parkinson’s disease.Neural Regen. Res.202318119419910.4103/1673‑5374.34389235799542
    [Google Scholar]
  110. ZhuD. LiangR. LiuY. LiZ. ChengL. RenJ. GuoY. WangM. ChaiH. NiuQ. YangS. BaiJ. YuH. ZhangH. QinX. Deferoxamine ameliorated Al(mal) 3 -induced neuronal ferroptosis in adult rats by chelating brain iron to attenuate oxidative damage.Toxicol. Mech. Methods202232753054110.1080/15376516.2022.205325435313783
    [Google Scholar]
  111. SunY. HeL. WangW. XieZ. ZhangX. WangP. WangL. YanC. LiuZ. ZhaoJ. CuiZ. WangY. TangL. ZhangZ. Activation of Atg7-dependent autophagy by a novel inhibitor of the Keap1–Nrf2 protein–protein interaction from Penthorum chinense Pursh. attenuates 6-hydroxydopamine-induced ferroptosis in zebrafish and dopaminergic neurons.Food Funct.202213147885790010.1039/D2FO00357K35776077
    [Google Scholar]
  112. YangS. xieZ. PeiT. zengY. XiongQ. WeiH. WangY. ChengW. Salidroside attenuates neuronal ferroptosis by activating the Nrf2/HO1 signaling pathway in Aβ1-42-induced Alzheimer’s disease mice and glutamate-injured HT22 cells.Chin. Med.20221718210.1186/s13020‑022‑00634‑335787281
    [Google Scholar]
  113. VoetS. SrinivasanS. LamkanfiM. van LooG. Inflammasomes in neuroinflammatory and neurodegenerative diseases.EMBO Mol. Med.2019116e1024810.15252/emmm.20181024831015277
    [Google Scholar]
  114. LiaoS. ApaijaiN. LuoY. WuJ. ChunchaiT. SinghanatK. ArunsakB. BenjanuwattraJ. ChattipakornN. ChattipakornS.C. Cell death inhibitors protect against brain damage caused by cardiac ischemia/reperfusion injury.Cell Death Discov.20217131210.1038/s41420‑021‑00698‑434689160
    [Google Scholar]
  115. KuangH. WangT. LiuL. TangC. LiT. LiuM. WangT. ZhongW. WangY. Treatment of early brain injury after subarachnoid hemorrhage in the rat model by inhibiting p53-induced ferroptosis.Neurosci. Lett.202176213613410.1016/j.neulet.2021.13613434311053
    [Google Scholar]
  116. McLachlanD. DaltonA.J. KruckT.P. BellM.Y. SmithW.L. KalowW. AndrewsD.F. Intramuscular desferrioxamine in patients with Alzheimer’s disease.Lancet199133787531304130810.1016/0140‑6736(91)92978‑B1674295
    [Google Scholar]
  117. ZhangY. HeM. Deferoxamine enhances alternative activation of microglia and inhibits amyloid beta deposits in APP/PS1 mice.Brain Res.20171677869210.1016/j.brainres.2017.09.01928963052
    [Google Scholar]
  118. RaoS.S. PortburyS.D. LagoL. BushA.I. AdlardP.A. The iron chelator deferiprone improves the phenotype in a mouse model of tauopathy.J. Alzheimers Dis.20207841783178710.3233/JAD‑20900933252085
    [Google Scholar]
/content/journals/ppl/10.2174/0109298665333926240927074528
Loading
/content/journals/ppl/10.2174/0109298665333926240927074528
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test