Skip to main content
SpringerLink
Log in

Ferroptosis in Nervous System Diseases

  • Chapter
  • First Online:
Ferroptosis in Health and Disease

Abstract

Ferroptosis is a non-apoptotic form of regulated cell death characterized by iron-dependent accumulation of lethal lipid peroxidation. First identified in cancer cells in 2012, ferroptosis has significant implications in several nervous system disorders. Studies have revealed the presence of iron accumulation, lipid peroxidation, glutathione reduction, and glutathione peroxidase 4 inhibition in various brain diseases, and ferroptotic inhibitors have been shown to protect neurons and improve cognitive function in experimental cellular and/or animal models. In this chapter, we describe the role that ferroptotic mechanisms play in different brain diseases and discuss how this knowledge can be harnessed to prevent and treat nervous system diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abrams RP, Carroll WL, Woerpel KA (2016) Five-membered ring peroxide selectively initiates ferroptosis in cancer cells. ACS Chem Biol 11:1305–1312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Adamczak SE, de Rivero Vaccari JP, Dale G, Brand FJ 3rd, Nonner D, Bullock MR, Dahl GP, Dietrich WD, Keane RW (2014) Pyroptotic neuronal cell death mediated by the AIM2 inflammasome. J Cereb Blood Flow Metab 34:621–629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ahmad S, Elsherbiny NM, Haque R, Khan MB, Ishrat T, Shah ZA, Khan MM, Ali M, Jamal A, Katare DP et al (2014) Sesamin attenuates neurotoxicity in mouse model of ischemic brain stroke. Neurotoxicology 45:100–110

    Article  CAS  PubMed  Google Scholar 

  • Au A, Griffiths LR, Irene L, Kooi CW, Wei LK (2017) The impact of APOA5, APOB, APOC3 and ABCA1 gene polymorphisms on ischemic stroke: evidence from a meta-analysis. Atherosclerosis 265:60–70

    Article  CAS  PubMed  Google Scholar 

  • Ayala A, Munoz MF, Arguelles S (2014) Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev 2014:360438

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ayton S, Lei P, Duce JA, Wong BX, Sedjahtera A, Adlard PA, Bush AI, Finkelstein DI (2013) Ceruloplasmin dysfunction and therapeutic potential for Parkinson disease. Ann Neurol 73:554–559

    Article  CAS  PubMed  Google Scholar 

  • Ayton S, Zhang M, Roberts BR, Lam LQ, Lind M, McLean C, Bush AI, Frugier T, Crack PJ, Duce JA (2014) Ceruloplasmin and beta-amyloid precursor protein confer neuroprotection in traumatic brain injury and lower neuronal iron. Free Radic Biol Med 69:331–337

    Article  CAS  PubMed  Google Scholar 

  • Back SA, Luo NL, Mallinson RA, O’Malley JP, Wallen LD, Frei B, Morrow JD, Petito CK, Roberts CT Jr, Murdoch GH, Montine TJ (2005) Selective vulnerability of preterm white matter to oxidative damage defined by F2-isoprostanes. Ann Neurol 58:108–120

    Article  CAS  PubMed  Google Scholar 

  • Baenziger O, Martin E, Steinlin M, Good M, Largo R, Burger R, Fanconi S, Duc G, Buchli R, Rumpel H et al (1993) Early pattern recognition in severe perinatal asphyxia: a prospective MRI study. Neuroradiology 35:437–442

    Article  CAS  PubMed  Google Scholar 

  • Bartlett WP, Li XS, Connor JR (1991) Expression of transferrin mRNA in the CNS of normal and jimpy mice. J Neurochem 57:318–322

    Article  CAS  PubMed  Google Scholar 

  • Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Chang AR, Cheng S, Das SR et al (2019) Heart disease and stroke statistics-2019 update: a report from the American Heart Association. Circulation CIR0000000000000659

    Google Scholar 

  • Brault S, Martinez-Bermudez AK, Roberts J 2nd, Cui QL, Fragoso G, Hemdan S, Liu HN, Gobeil F Jr, Quiniou C, Kermorvant-Duchemin E et al (2004) Cytotoxicity of the E(2)-isoprostane 15-E(2t)-IsoP on oligodendrocyte progenitors. Free Radic Biol Med 37:358–366

    Article  CAS  PubMed  Google Scholar 

  • Browne SE, Ferrante RJ, Beal MF (1999) Oxidative stress in Huntington’s disease. Brain Pathol 9:147–163

    Article  CAS  PubMed  Google Scholar 

  • Cao JY, Dixon SJ (2016) Mechanisms of ferroptosis. Cell Mol Life Sci 73:2195–2209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cassarino DS, Fall CP, Swerdlow RH, Smith TS, Halvorsen EM, Miller SW, Parks JP, Parker WD Jr, Bennett JP Jr (1997) Elevated reactive oxygen species and antioxidant enzyme activities in animal and cellular models of Parkinson’s disease. Biochim Biophys Acta 1362:77–86

    Article  CAS  PubMed  Google Scholar 

  • Castellani RJ, Moreira PI, Liu G, Dobson J, Perry G, Smith MA, Zhu X (2007) Iron: the Redox-active center of oxidative stress in Alzheimer disease. Neurochem Res 32:1640–1645

    Article  CAS  PubMed  Google Scholar 

  • Ceschin R, Lee VK, Schmithorst V, Panigrahy A (2015) Regional vulnerability of longitudinal cortical association connectivity: associated with structural network topology alterations in preterm children with cerebral palsy. Neuroimage Clin 9:322–337

    Article  PubMed  PubMed Central  Google Scholar 

  • Chang CF, Cho S, Wang J (2014) (−)-Epicatechin protects hemorrhagic brain via synergistic Nrf2 pathways. Ann Clin Transl Neurol 1:258–271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen CM, Wu YR, Cheng ML, Liu JL, Lee YM, Lee PW, Soong BW, Chiu DT (2007) Increased oxidative damage and mitochondrial abnormalities in the peripheral blood of Huntington’s disease patients. Biochem Biophys Res Commun 359:335–340

    Article  CAS  PubMed  Google Scholar 

  • Chen J, Marks E, Lai B, Zhang Z, Duce JA, Lam LQ, Volitakis I, Bush AI, Hersch S, Fox JH (2013) Iron accumulates in Huntington’s disease neurons: protection by deferoxamine. PLoS One 8:e77023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen L, Hambright WS, 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chmatalova Z, Vyhnalek M, Laczo J, Hort J, Pospisilova R, Pechova M, Skoumalova A (2017) Relation of plasma selenium and lipid peroxidation end products in patients with Alzheimer’s disease. Physiol Res 66:1049–1056

    CAS  PubMed  Google Scholar 

  • Codazzi F, Pelizzoni I, Zacchetti D, Grohovaz F (2015) Iron entry in neurons and astrocytes: a link with synaptic activity. Front Mol Neurosci 8:18

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Codazzi F, Hu A, Rai M, Donatello S, Salerno Scarzella F, Mangiameli E, Pelizzoni I, Grohovaz F, Pandolfo M (2016) Friedreich ataxia-induced pluripotent stem cell-derived neurons show a cellular phenotype that is corrected by a benzamide HDAC inhibitor. Hum Mol Genet 25:4847–4855

    CAS  PubMed  Google Scholar 

  • Collins A (2013) Clinical neurogenetics: friedreich ataxia. Neurol Clin 31:1095–1120

    Article  PubMed  Google Scholar 

  • Cotman CW, Anderson AJ (1995) A potential role for apoptosis in neurodegeneration and Alzheimer’s disease. Mol Neurobiol 10:19–45

    Article  CAS  PubMed  Google Scholar 

  • Cotticelli MG, Crabbe AM, Wilson RB, Shchepinov MS (2013) Insights into the role of oxidative stress in the pathology of Friedreich ataxia using peroxidation resistant polyunsaturated fatty acids. Redox Biol 1:398–404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cotticelli MG, Xia S, Lin D, Lee T, Terrab L, Wipf P, Huryn DM, Wilson RB (2019) Ferroptosis as a novel therapeutic target for Friedreich’s Ataxia. J Pharmacol Exp Ther 369:47–54

    Article  CAS  PubMed  Google Scholar 

  • Crapper McLachlan DR, Dalton AJ, Kruck TP, Bell MY, Smith WL, Kalow W, Andrews DF (1991) Intramuscular desferrioxamine in patients with Alzheimer’s disease. Lancet 337:1304–1308

    Article  CAS  PubMed  Google Scholar 

  • Cui Z, Zhong Z, Yang Y, Wang B, Sun Y, Sun Q, Yang GY, Bian L (2016) Ferrous iron induces Nrf2 expression in mouse brain astrocytes to prevent neurotoxicity. J Biochem Mol Toxicol 30:396–403

    Article  CAS  PubMed  Google Scholar 

  • Davis S, Helfaer MA, Traystman RJ, Hurn PD (1997) Parallel antioxidant and antiexcitotoxic therapy improves outcome after incomplete global cerebral ischemia in dogs. Stroke 28:198–204. discussion 204-195

    Article  CAS  PubMed  Google Scholar 

  • Devos D, Moreau C, Devedjian JC, Kluza J, Petrault M, Laloux C, Jonneaux A, Ryckewaert G, Garcon G, Rouaix N et al (2014) Targeting chelatable iron as a therapeutic modality in Parkinson’s disease. Antioxid Redox Signal 21:195–210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dexter D, Carter C, Agid F, Agid Y, Lees AJ, Jenner P, Marsden CD (1986) Lipid peroxidation as cause of nigral cell death in Parkinson’s disease. Lancet 2:639–640

    Article  CAS  PubMed  Google Scholar 

  • Dexter DT, Wells FR, Agid F, Agid Y, Lees AJ, Jenner P, Marsden CD (1987) Increased nigral iron content in postmortem parkinsonian brain. Lancet 2:1219–1220

    Article  CAS  PubMed  Google Scholar 

  • Di Pietro V, Lazzarino G, Amorini AM, Tavazzi B, D’Urso S, Longo S, Vagnozzi R, Signoretti S, Clementi E, Giardina B et al (2014) Neuroglobin expression and oxidant/antioxidant balance after graded traumatic brain injury in the rat. Free Radic Biol Med 69:258–264

    Article  PubMed  CAS  Google Scholar 

  • Dietrich RB, Bradley WG Jr (1988) Iron accumulation in the basal ganglia following severe ischemic-anoxic insults in children. Radiology 168:203–206

    Article  CAS  PubMed  Google Scholar 

  • Ding H, Yan CZ, Shi H, Zhao YS, Chang SY, Yu P, Wu WS, Zhao CY, Chang YZ, Duan XL (2011) Hepcidin is involved in iron regulation in the ischemic brain. PLoS One 6:e25324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dixon SJ (2017) Ferroptosis: bug or feature? Immunol Rev 277:150–157

    Article  CAS  PubMed  Google Scholar 

  • Dixon SJ, Stockwell BR (2019) The hallmarks of ferroptosis. Annu Rev Cancer Biol 3:35–54

    Article  Google Scholar 

  • Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS et al (2012) Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149:1060–1072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dixon SJ, Winter GE, Musavi LS, Lee ED, Snijder B, Rebsamen M, Superti-Furga G, Stockwell BR (2015) Human haploid cell genetics reveals roles for lipid metabolism genes in nonapoptotic cell death. ACS Chem Biol 10:1604–1609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Do Van B, Gouel F, Jonneaux A, Timmerman K, Gele P, Petrault M, Bastide M, Laloux C, Moreau C, Bordet R et al (2016) Ferroptosis, a newly characterized form of cell death in Parkinson’s disease that is regulated by PKC. Neurobiol Dis 94:169–178

    Article  CAS  PubMed  Google Scholar 

  • Doll S, Proneth B, Tyurina YY, Panzilius E, Kobayashi S, Ingold I, Irmler M, Beckers J, Aichler M, Walch A et al (2017) ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat Chem Biol 13:91–98

    Article  CAS  PubMed  Google Scholar 

  • Dolma S, Lessnick SL, Hahn WC, Stockwell BR (2003) Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell 3:285–296

    Article  CAS  PubMed  Google Scholar 

  • Eberhard Y, McDermott SP, Wang X, Gronda M, Venugopal A, Wood TE, Hurren R, Datti A, Batey RA, Wrana J et al (2009) Chelation of intracellular iron with the antifungal agent ciclopirox olamine induces cell death in leukemia and myeloma cells. Blood 114:3064–3073

    Article  CAS  PubMed  Google Scholar 

  • Eling N, Reuter L, Hazin J, Hamacher-Brady A, Brady NR (2015) Identification of artesunate as a specific activator of ferroptosis in pancreatic cancer cells. Oncoscience 2:517–532

    Article  PubMed  PubMed Central  Google Scholar 

  • Fang KM, Cheng FC, Huang YL, Chung SY, Jian ZY, Lin MC (2013) Trace element, antioxidant activity, and lipid peroxidation levels in brain cortex of gerbils after cerebral ischemic injury. Biol Trace Elem Res 152:66–74

    Article  CAS  PubMed  Google Scholar 

  • Fearnley JM, Lees AJ (1991) Ageing and Parkinson’s disease: substantia nigra regional selectivity. Brain 114(Pt 5):2283–2301

    Article  PubMed  Google Scholar 

  • Feng H, Stockwell BR (2018) Unsolved mysteries: how does lipid peroxidation cause ferroptosis? PLoS Biol 16:e2006203

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Friedmann Angeli JP, Schneider M, Proneth B, Tyurina YY, Tyurin VA, Hammond VJ, Herbach N, Aichler M, Walch A, Eggenhofer E et al (2014) Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat Cell Biol 16:1180–1191

    Article  CAS  PubMed  Google Scholar 

  • Gajowiak A, Stys A, Starzynski RR, Staron R, Lipinski P (2016) Misregulation of iron homeostasis in amyotrophic lateral sclerosis. Postepy Hig Med Dosw (Online) 70:709–721

    Article  Google Scholar 

  • Galluzzi L, Bravo-San Pedro JM, Vitale I, Aaronson SA, Abrams JM, Adam D, Alnemri ES, Altucci L, Andrews D, Annicchiarico-Petruzzelli M et al (2015) Essential versus accessory aspects of cell death: recommendations of the NCCD 2015. Cell Death Differ 22:58–73

    Article  CAS  PubMed  Google Scholar 

  • Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, Alnemri ES, Altucci L, Amelio I, Andrews DW et al (2018) Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ 25:486–541

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ghosh D, Levault KR, Brewer GJ (2014) Relative importance of redox buffers GSH and NAD(P)H in age-related neurodegeneration and Alzheimer disease-like mouse neurons. Aging Cell 13:631–640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gomes CM, Santos R (2013) Neurodegeneration in Friedreich’s ataxia: from defective frataxin to oxidative stress. Oxid Med Cell Longev 2013:487534

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gordon PH, Moore DH, Miller RG, Florence JM, Verheijde JL, Doorish C, Hilton JF, Spitalny GM, MacArthur RB, Mitsumoto H et al (2007) Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial. Lancet Neurol 6:1045–1053

    Article  CAS  PubMed  Google Scholar 

  • Greenshields AL, Shepherd TG, Hoskin DW (2017) Contribution of reactive oxygen species to ovarian cancer cell growth arrest and killing by the anti-malarial drug artesunate. Mol Carcinog 56:75–93

    Article  CAS  PubMed  Google Scholar 

  • Grolez G, Moreau C, Sablonniere B, Garcon G, Devedjian JC, Meguig S, Gele P, Delmaire C, Bordet R, Defebvre L et al (2015) Ceruloplasmin activity and iron chelation treatment of patients with Parkinson’s disease. BMC Neurol 15:74

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Grondin R, Kaytor MD, Ai Y, Nelson PT, Thakker DR, Heisel J, Weatherspoon MR, Blum JL, Burright EN, Zhang Z, Kaemmerer WF (2012) Six-month partial suppression of Huntingtin is well tolerated in the adult rhesus striatum. Brain 135:1197–1209

    Article  PubMed  PubMed Central  Google Scholar 

  • Guo J, Xu B, Han Q, Zhou H, Xia Y, Gong C, Dai X, Li Z, Wu G (2018) Ferroptosis: a novel anti-tumor action for cisplatin. Cancer Res Treat 50:445–460

    Article  CAS  PubMed  Google Scholar 

  • Hambright WS, Fonseca RS, 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hanson LR, Roeytenberg A, Martinez PM, Coppes VG, Sweet DC, Rao RJ, Marti DL, Hoekman JD, Matthews RB, Frey WH 2nd, Panter SS (2009) Intranasal deferoxamine provides increased brain exposure and significant protection in rat ischemic stroke. J Pharmacol Exp Ther 330:679–686

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hider RC, Kong XL (2011) Glutathione: a key component of the cytoplasmic labile iron pool. Biometals 24:1179–1187

    Article  CAS  PubMed  Google Scholar 

  • Hirayama T, Nagasawa H (2017) Chemical tools for detecting Fe ions. J Clin Biochem Nutr 60:39–48

    Article  CAS  PubMed  Google Scholar 

  • Hou W, Xie Y, Song X, Sun X, Lotze MT, Zeh HJ 3rd, Kang R, Tang D (2016) Autophagy promotes ferroptosis by degradation of ferritin. Autophagy 12:1425–1428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang HS, Chen CJ, Suzuki H, Yamamoto S, Chang WC (1999) Inhibitory effect of phospholipid hydroperoxide glutathione peroxidase on the activity of lipoxygenases and cyclooxygenases. Prostaglandins Other Lipid Mediat 58:65–75

    Article  CAS  PubMed  Google Scholar 

  • Inder T, Mocatta T, Darlow B, Spencer C, Volpe JJ, Winterbourn C (2002) Elevated free radical products in the cerebrospinal fluid of VLBW infants with cerebral white matter injury. Pediatr Res 52:213–218

    Article  CAS  PubMed  Google Scholar 

  • Ingold I, Berndt C, Schmitt S, Doll S, Poschmann G, Buday K, Roveri A, Peng X, Porto Freitas F, Seibt T et al (2018) Selenium utilization by GPX4 is required to prevent hydroperoxide-induced ferroptosis. Cell 172:409–422 e421

    Article  CAS  PubMed  Google Scholar 

  • Ishii T, Warabi E, Mann GE (2019) Circadian control of BDNF-mediated Nrf2 activation in astrocytes protects dopaminergic neurons from ferroptosis. Free Radic Biol Med 133:169–178

    Article  CAS  PubMed  Google Scholar 

  • Jennis M, Kung CP, Basu S, Budina-Kolomets A, Leu JI, Khaku S, Scott JP, Cai KQ, Campbell MR, Porter DK et al (2016) An African-specific polymorphism in the TP53 gene impairs p53 tumor suppressor function in a mouse model. Genes Dev 30:918–930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jia F, Mao Q, Liang YM, Jiang JY (2009) Effect of post-traumatic mild hypothermia on hippocampal cell death after traumatic brain injury in rats. J Neurotrauma 26:243–252

    Article  PubMed  Google Scholar 

  • Jimenez-Sanchez M, Licitra F, Underwood BR, Rubinsztein DC (2017) Huntington’s disease: mechanisms of pathogenesis and therapeutic strategies. Cold Spring Harb Perspect Med 7:a024240

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Johnson WM, Wilson-Delfosse AL, Mieyal JJ (2012) Dysregulation of glutathione homeostasis in neurodegenerative diseases. Nutrients 4:1399–1440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kabiraj P, Valenzuela CA, Marin JE, Ramirez DA, Mendez L, Hwang MS, Varela-Ramirez A, Fenelon K, Narayan M, Skouta R (2015) The neuroprotective role of ferrostatin-1 under rotenone-induced oxidative stress in dopaminergic neuroblastoma cells. Protein J 34:349–358

    Article  CAS  PubMed  Google Scholar 

  • Kagan VE, Mao G, Qu F, Angeli JP, Doll S, Croix CS, Dar HH, Liu B, Tyurin VA, Ritov VB et al (2017) Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. Nat Chem Biol 13:81–90

    Article  CAS  PubMed  Google Scholar 

  • Kang R, Tang D (2017) Autophagy and ferroptosis – what’s the connection? Curr Pathobiol Rep 5:153–159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khalaf S, Ahmad AS, Chamara K, Dore S (2018) Unique properties associated with the brain penetrant iron chelator HBED reveal remarkable beneficial effects after brain trauma. J Neurotrauma. https://doi.org/10.1089/neu.2017.5617

    Article  Google Scholar 

  • Khandelwal PJ, Herman AM, Moussa CE (2011) Inflammation in the early stages of neurodegenerative pathology. J Neuroimmunol 238:1–11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klepac N, Relja M, Klepac R, Hecimovic S, Babic T, Trkulja V (2007) Oxidative stress parameters in plasma of Huntington’s disease patients, asymptomatic Huntington’s disease gene carriers and healthy subjects: a cross-sectional study. J Neurol 254:1676–1683

    Article  CAS  PubMed  Google Scholar 

  • Koeppen AH, Mazurkiewicz JE (2013) Friedreich ataxia: neuropathology revised. J Neuropathol Exp Neurol 72:78–90

    Article  CAS  PubMed  Google Scholar 

  • Kondo Y, Ogawa N, Asanuma M, Ota Z, Mori A (1995) Regional differences in late-onset iron deposition, ferritin, transferrin, astrocyte proliferation, and microglial activation after transient forebrain ischemia in rat brain. J Cereb Blood Flow Metab 15:216–226

    Article  CAS  PubMed  Google Scholar 

  • Kondo Y, Asanuma M, Nishibayashi S, Iwata E, Ogawa N (1997) Late-onset lipid peroxidation and neuronal cell death following transient forebrain ischemia in rat brain. Brain Res 772:37–44

    Article  CAS  PubMed  Google Scholar 

  • Kontos HA (2001) Oxygen radicals in cerebral ischemia: the 2001 Willis lecture. Stroke 32:2712–2716

    Article  CAS  PubMed  Google Scholar 

  • Kontos CD, Wei EP, Williams JI, Kontos HA, Povlishock JT (1992) Cytochemical detection of superoxide in cerebral inflammation and ischemia in vivo. Am J Phys 263:H1234–H1242

    Article  CAS  Google Scholar 

  • Lee J, Kosaras B, Del Signore SJ, Cormier K, McKee A, Ratan RR, Kowall NW, Ryu H (2011) Modulation of lipid peroxidation and mitochondrial function improves neuropathology in Huntington’s disease mice. Acta Neuropathol 121:487–498

    Article  CAS  PubMed  Google Scholar 

  • Lei P, Ayton S, Finkelstein DI, Spoerri L, Ciccotosto GD, Wright DK, Wong BX, Adlard PA, Cherny RA, Lam LQ et al (2012) Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export. Nat Med 18:291–295

    Article  CAS  PubMed  Google Scholar 

  • Lewerenz J, Ates G, Methner A, Conrad M, Maher P (2018) Oxytosis/ferroptosis-(re-) emerging roles for oxidative stress-dependent non-apoptotic cell death in diseases of the central nervous system. Front Neurosci 12:214

    Article  PubMed  PubMed Central  Google Scholar 

  • Li Q, Han X, Lan X, Gao Y, Wan J, Durham F, Cheng T, Yang J, Wang Z, Jiang C et al (2017a) Inhibition of neuronal ferroptosis protects hemorrhagic brain. JCI Insight 2:e90777

    Article  PubMed  PubMed Central  Google Scholar 

  • Li Q, Wan J, Lan X, Han X, Wang Z, Wang J (2017b) Neuroprotection of brain-permeable iron chelator VK-28 against intracerebral hemorrhage in mice. J Cereb Blood Flow Metab 37:3110–3123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Q, Weiland A, Chen X, Lan X, Han X, Durham F, Liu X, Wan J, Ziai WC, Hanley DF, Wang J (2018) Ultrastructural characteristics of neuronal death and white matter injury in mouse brain tissues after intracerebral hemorrhage: coexistence of ferroptosis, autophagy, and necrosis. Front Neurol 9:581

    Article  PubMed  PubMed Central  Google Scholar 

  • Linkermann A, Skouta R, Himmerkus N, Mulay SR, Dewitz C, De Zen F, Prokai A, Zuchtriegel G, Krombach F, Welz PS et al (2014) Synchronized renal tubular cell death involves ferroptosis. Proc Natl Acad Sci USA 111:16836–16841

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lipscomb DC, Gorman LG, Traystman RJ, Hurn PD (1998) Low molecular weight iron in cerebral ischemic acidosis in vivo. Stroke 29:487–492. Discussion 493

    Article  CAS  PubMed  Google Scholar 

  • Liu T, Zhao DX, Cui H, Chen L, Bao YH, Wang Y, Jiang JY (2016) Therapeutic hypothermia attenuates tissue damage and cytokine expression after traumatic brain injury by inhibiting necroptosis in the rat. Sci Rep 6:24547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu L, Huang W, Wang J, Song H, Cen J, Ji B (2017) Anthraquinone derivative exerted hormetic effect on the apoptosis in oxygen-glucose deprivation-induced PC12 cells via ERK and Akt activated Nrf2/HO-1 signaling pathway. Chem Biol Interact 262:1–11

    Article  CAS  PubMed  Google Scholar 

  • Lou M, Lieb K, Selim M (2009) The relationship between hematoma iron content and perihematoma edema: an MRI study. Cerebrovasc Dis 27:266–271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu L, Cao H, Wei X, Li Y, Li W (2015) Iron deposition is positively related to cognitive impairment in patients with chronic mild traumatic brain injury: assessment with susceptibility weighted imaging. Biomed Res Int 2015:470676

    PubMed  PubMed Central  Google Scholar 

  • Ma MW, Wang J, Zhang Q, Wang R, Dhandapani KM, Vadlamudi RK, Brann DW (2017) NADPH oxidase in brain injury and neurodegenerative disorders. Mol Neurodegener 12:7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • MacLeod AK, McMahon M, Plummer SM, Higgins LG, Penning TM, Igarashi K, Hayes JD (2009) Characterization of the cancer chemopreventive NRF2-dependent gene battery in human keratinocytes: demonstration that the KEAP1-NRF2 pathway, and not the BACH1-NRF2 pathway, controls cytoprotection against electrophiles as well as redox-cycling compounds. Carcinogenesis 30:1571–1580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maher P (2018) Potentiation of glutathione loss and nerve cell death by the transition metals iron and copper: implications for age-related neurodegenerative diseases. Free Radic Biol Med 115:92–104

    Article  CAS  PubMed  Google Scholar 

  • Mandal PK, 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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Mattson MP (2006) Neuronal life-and-death signaling, apoptosis, and neurodegenerative disorders. Antioxid Redox Signal 8:1997–2006

    Article  CAS  PubMed  Google Scholar 

  • McBride JL, Pitzer MR, Boudreau RL, Dufour B, Hobbs T, Ojeda SR, Davidson BL (2011) Preclinical safety of RNAi-mediated HTT suppression in the rhesus macaque as a potential therapy for Huntington’s disease. Mol Ther 19:2152–2162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mehdiratta M, Kumar S, Hackney D, Schlaug G, Selim M (2008) Association between serum ferritin level and perihematoma edema volume in patients with spontaneous intracerebral hemorrhage. Stroke 39:1165–1170

    Article  CAS  PubMed  Google Scholar 

  • Mel’nikov OF (1985) Method of isolating leukocytes from the peripheral blood. Lab Delo 632–633

    Google Scholar 

  • Mi Y, Gao X, Xu H, Cui Y, Zhang Y, Gou X (2019) The emerging roles of ferroptosis in Huntington’s disease. Neuromolecular Med 21:110–119

    Article  CAS  PubMed  Google Scholar 

  • Miyamoto M, Murphy TH, Schnaar RL, Coyle JT (1989) Antioxidants protect against glutamate-induced cytotoxicity in a neuronal cell line. J Pharmacol Exp Ther 250:1132–1140

    CAS  PubMed  Google Scholar 

  • Moore DJ, West AB, Dawson VL, Dawson TM (2005) Molecular pathophysiology of Parkinson’s disease. Annu Rev Neurosci 28:57–87

    Article  CAS  PubMed  Google Scholar 

  • Moreau C, Danel V, Devedjian JC, Grolez G, Timmerman K, Laloux C, Petrault M, Gouel F, Jonneaux A, Dutheil M et al (2018) Could conservative iron chelation lead to neuroprotection in amyotrophic lateral sclerosis? Antioxid Redox Signal 29:742–748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nelson CW, Wei EP, Povlishock JT, Kontos HA, Moskowitz MA (1992) Oxygen radicals in cerebral ischemia. Am J Physiol 263:H1356–H1362

    CAS  PubMed  Google Scholar 

  • Park SW, Kim SH, Park KH, Kim SD, Kim JY, Baek SY, Chung BS, Kang CD (2004) Preventive effect of antioxidants in MPTP-induced mouse model of Parkinson’s disease. Neurosci Lett 363:243–246

    Article  CAS  PubMed  Google Scholar 

  • Park UJ, Lee YA, Won SM, Lee JH, Kang SH, Springer JE, Lee YB, Gwag BJ (2011) Blood-derived iron mediates free radical production and neuronal death in the hippocampal CA1 area following transient forebrain ischemia in rat. Acta Neuropathol 121:459–473

    Article  CAS  PubMed  Google Scholar 

  • Parkinson Study Group PI (2007) Mixed lineage kinase inhibitor CEP-1347 fails to delay disability in early Parkinson disease. Neurology 69:1480–1490

    Article  CAS  Google Scholar 

  • Patt A, Horesh IR, Berger EM, Harken AH, Repine JE (1990) Iron depletion or chelation reduces ischemia/reperfusion-induced edema in gerbil brains. J Pediatr Surg 25:224–227. discussion 227–228

    Article  CAS  PubMed  Google Scholar 

  • Perez de la Ossa N, Sobrino T, Silva Y, Blanco M, Millan M, Gomis M, Agulla J, Araya P, Reverte S, Serena J, Davalos A (2010) Iron-related brain damage in patients with intracerebral hemorrhage. Stroke 41:810–813

    Article  PubMed  CAS  Google Scholar 

  • Perry TL, Yong VW, Clavier RM, Jones K, Wright JM, Foulks JG, Wall RA (1985) Partial protection from the dopaminergic neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by four different antioxidants in the mouse. Neurosci Lett 60:109–114

    Article  CAS  PubMed  Google Scholar 

  • Petillon C, Hergesheimer R, Puy H, Corcia P, Vourc’h P, Andres C, Karim Z, Blasco H (2018) The relevancy of data regarding the metabolism of iron to our understanding of deregulated mechanisms in ALS; hypotheses and pitfalls. Front Neurosci 12:1031

    Article  PubMed  Google Scholar 

  • Pichler I, Del Greco MF, Gogele M, Lill CM, Bertram L, Do CB, Eriksson N, Foroud T, Myers RH, Consortium PG et al (2013) Serum iron levels and the risk of Parkinson disease: a Mendelian randomization study. PLoS Med 10:e1001462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prass K, Ruscher K, Karsch M, Isaev N, Megow D, Priller J, Scharff A, Dirnagl U, Meisel A (2002) Desferrioxamine induces delayed tolerance against cerebral ischemia in vivo and in vitro. J Cereb Blood Flow Metab 22:520–525

    Article  CAS  PubMed  Google Scholar 

  • Pratico D, Sung S (2004) Lipid peroxidation and oxidative imbalance: early functional events in Alzheimer’s disease. J Alzheimers Dis 6:171–175

    Article  CAS  PubMed  Google Scholar 

  • Proneth B, Conrad M (2019) Ferroptosis and necroinflammation, a yet poorly explored link. Cell Death Differ 26:14–24

    Article  CAS  PubMed  Google Scholar 

  • Raz E, Jensen JH, Ge Y, Babb JS, Miles L, Reaume J, Grossman RI, Inglese M (2011) Brain iron quantification in mild traumatic brain injury: a magnetic field correlation study. AJNR Am J Neuroradiol 32:1851–1856

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reed TT, Pierce WM, Markesbery WR, Butterfield DA (2009) Proteomic identification of HNE-bound proteins in early Alzheimer disease: insights into the role of lipid peroxidation in the progression of AD. Brain Res 1274:66–76

    Article  CAS  PubMed  Google Scholar 

  • Rinne JO, Rummukainen J, Paljarvi L, Sako E, Molsa P, Rinne UK (1989) Neuronal loss in the substantia nigra in patients with Alzheimer’s disease and Parkinson’s disease in relation to extrapyramidal symptoms and dementia. Prog Clin Biol Res 317:325–332

    CAS  PubMed  Google Scholar 

  • Rosas HD, Chen YI, Doros G, Salat DH, Chen NK, Kwong KK, Bush A, Fox J, Hersch SM (2012) Alterations in brain transition metals in Huntington disease: an evolving and intricate story. Arch Neurol 69:887–893

    Article  PubMed  PubMed Central  Google Scholar 

  • Salvador GA (2010) Iron in neuronal function and dysfunction. Biofactors 36:103–110

    Article  CAS  PubMed  Google Scholar 

  • Seiler A, Schneider M, Forster H, Roth S, Wirth EK, Culmsee C, Plesnila N, Kremmer E, Radmark O, Wurst W et al (2008) Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death. Cell Metab 8:237–248

    Article  CAS  PubMed  Google Scholar 

  • Selim MH, Ratan RR (2004) The role of iron neurotoxicity in ischemic stroke. Ageing Res Rev 3:345–353

    Article  CAS  PubMed  Google Scholar 

  • Seol Y, Zhang H, Agama K, Lorence N, Pommier Y, Neuman KC (2015) Single-molecule supercoil relaxation assay as a screening tool to determine the mechanism and efficacy of human topoisomerase IB inhibitors. Mol Cancer Ther 14:2552–2559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shimada K, Hayano M, Pagano NC, Stockwell BR (2016a) Cell-line selectivity improves the predictive power of pharmacogenomic analyses and helps identify NADPH as biomarker for ferroptosis sensitivity. Cell Chem Biol 23:225–235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shimada K, Skouta R, Kaplan A, Yang WS, Hayano M, Dixon SJ, Brown LM, Valenzuela CA, Wolpaw AJ, Stockwell BR (2016b) Global survey of cell death mechanisms reveals metabolic regulation of ferroptosis. Nat Chem Biol 12:497–503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sian J, Dexter DT, Lees AJ, Daniel S, Agid Y, Javoy-Agid F, Jenner P, Marsden CD (1994) Alterations in glutathione levels in Parkinson’s disease and other neurodegenerative disorders affecting basal ganglia. Ann Neurol 36:348–355

    Article  CAS  PubMed  Google Scholar 

  • Simpson EP, Henry YK, Henkel JS, Smith RG, Appel SH (2004) Increased lipid peroxidation in sera of ALS patients: a potential biomarker of disease burden. Neurology 62:1758–1765

    Article  CAS  PubMed  Google Scholar 

  • Skouta R, Dixon SJ, Wang J, Dunn DE, Orman M, Shimada K, Rosenberg PA, Lo DC, Weinberg JM, Linkermann A, Stockwell BR (2014) Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models. J Am Chem Soc 136:4551–4556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song X, Zhu S, Chen P, Hou W, Wen Q, Liu J, Xie Y, Liu J, Klionsky DJ, Kroemer G et al (2018) AMPK-mediated BECN1 phosphorylation promotes ferroptosis by directly blocking system Xc(−) activity. Curr Biol 28:2388–2399.e2385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Speer RE, Karuppagounder SS, Basso M, Sleiman SF, Kumar A, Brand D, Smirnova N, Gazaryan I, Khim SJ, Ratan RR (2013) Hypoxia-inducible factor prolyl hydroxylases as targets for neuroprotection by “antioxidant” metal chelators: from ferroptosis to stroke. Free Radic Biol Med 62:26–36

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stockwell BR, Friedmann Angeli JP, Bayir H, Bush AI, Conrad M, Dixon SJ, Fulda S, Gascon S, Hatzios SK, Kagan VE et al (2017) Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell 171:273–285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun X, Niu X, Chen R, He W, Chen D, Kang R, Tang D (2016a) Metallothionein-1G facilitates sorafenib resistance through inhibition of ferroptosis. Hepatology 64:488–500

    Article  CAS  PubMed  Google Scholar 

  • Sun X, Ou Z, Chen R, Niu X, Chen D, Kang R, Tang D (2016b) Activation of the p62-Keap1-NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells. Hepatology 63:173–184

    Article  CAS  PubMed  Google Scholar 

  • Tuo QZ, Lei P, Jackman KA, Li XL, Xiong H, Li XL, Liuyang ZY, Roisman L, Zhang ST, Ayton S et al (2017) Tau-mediated iron export prevents ferroptotic damage after ischemic stroke. Mol Psychiatry 22:1520–1530

    Article  CAS  PubMed  Google Scholar 

  • Ursini F, Maiorino M, Valente M, Ferri L, Gregolin C (1982) Purification from pig liver of a protein which protects liposomes and biomembranes from peroxidative degradation and exhibits glutathione peroxidase activity on phosphatidylcholine hydroperoxides. Biochim Biophys Acta 710:197–211

    Article  CAS  PubMed  Google Scholar 

  • Veyrat-Durebex C, Corcia P, Mucha A, Benzimra S, Mallet C, Gendrot C, Moreau C, Devos D, Piver E, Pages JC et al (2014) Iron metabolism disturbance in a French cohort of ALS patients. Biomed Res Int 2014:485723

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vinceti M, Chiari A, Eichmuller M, Rothman KJ, Filippini T, Malagoli C, Weuve J, Tondelli M, Zamboni G, Nichelli PF, Michalke B (2017) A selenium species in cerebrospinal fluid predicts conversion to Alzheimer’s dementia in persons with mild cognitive impairment. Alzheimers Res Ther 9:100

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Volpe JJ, Kinney HC, Jensen FE, Rosenberg PA (2011) Reprint of “The developing oligodendrocyte: key cellular target in brain injury in the premature infant”. Int J Dev Neurosci 29:565–582

    Article  PubMed  Google Scholar 

  • Wan J, Ren H, Wang J (2019) Iron toxicity, lipid peroxidation and ferroptosis after intracerebral haemorrhage. Stroke Vasc Neurol. svn-2018-000205

    Google Scholar 

  • Wang J (2010) Preclinical and clinical research on inflammation after intracerebral hemorrhage. Prog Neurobiol 92:463–477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang X, Wang W, Li L, Perry G, Lee HG, Zhu X (2014) Oxidative stress and mitochondrial dysfunction in Alzheimer’s disease. Biochim Biophys Acta 1842:1240–1247

    Article  CAS  PubMed  Google Scholar 

  • Weiland A, Wang Y, Wu W, Lan X, Han X, Li Q, Wang J (2018) Ferroptosis and its role in diverse brain diseases. Mol Neurobiol. https://doi.org/10.1007/s12035-12018-11403-12033

  • Welin AK, Svedin P, Lapatto R, Sultan B, Hagberg H, Gressens P, Kjellmer I, Mallard C (2007) Melatonin reduces inflammation and cell death in white matter in the mid-gestation fetal sheep following umbilical cord occlusion. Pediatr Res 61:153–158

    Article  CAS  PubMed  Google Scholar 

  • Wenzel SE, Tyurina YY, Zhao J, St Croix CM, Dar HH, Mao G, Tyurin VA, Anthonymuthu TS, Kapralov AA, Amoscato AA et al (2017) PEBP1 wardens ferroptosis by enabling lipoxygenase generation of lipid death signals. Cell 171:628–641.e626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wirth EK, Conrad M, Winterer J, Wozny C, Carlson BA, Roth S, Schmitz D, Bornkamm GW, Coppola V, Tessarollo L et al (2010) Neuronal selenoprotein expression is required for interneuron development and prevents seizures and neurodegeneration. FASEB J 24:844–852

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu J, Hua Y, Keep RF, Nakamura T, Hoff JT, Xi G (2003) Iron and iron-handling proteins in the brain after intracerebral hemorrhage. Stroke 34:2964–2969

    Article  CAS  PubMed  Google Scholar 

  • Wu H, Wu T, Xu X, Wang J, Wang J (2011) Iron toxicity in mice with collagenase-induced intracerebral hemorrhage. J Cereb Blood Flow Metab 31:1243–1250

    Article  CAS  PubMed  Google Scholar 

  • Wu H, Wu T, Li M, Wang J (2012) Efficacy of the lipid-soluble iron chelator 2,2′-dipyridyl against hemorrhagic brain injury. Neurobiol Dis 45:388–394

    Article  CAS  PubMed  Google Scholar 

  • Xi G, Keep RF, Hoff JT (2006) Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol 5:53–63

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xie BS, Wang YQ, Lin Y, Mao Q, Feng JF, Gao GY, Jiang JY (2018) Inhibition of ferroptosis attenuates tissue damage and improves long-term outcomes after traumatic brain injury in mice. CNS Neurosci Ther. https://doi.org/10.1111/cns.13069

    Article  CAS  Google Scholar 

  • Xiong XY, Wang J, Qian ZM, Yang QW (2014) Iron and intracerebral hemorrhage: from mechanism to translation. Transl Stroke Res 5:429–441

    Article  CAS  PubMed  Google Scholar 

  • Xu J, Wang H, Ding K, Zhang L, Wang C, Li T, Wei W, Lu X (2014) Luteolin provides neuroprotection in models of traumatic brain injury via the Nrf2-ARE pathway. Free Radic Biol Med 71:186–195

    Article  CAS  PubMed  Google Scholar 

  • Yang WS, Stockwell BR (2016) Ferroptosis: death by lipid peroxidation. Trends Cell Biol 26:165–176

    Article  CAS  PubMed  Google Scholar 

  • Yang WS, SriRamaratnam R, Welsch ME, Shimada K, Skouta R, Viswanathan VS, Cheah JH, Clemons PA, Shamji AF, Clish CB et al (2014) Regulation of ferroptotic cancer cell death by GPX4. Cell 156:317–331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuan H, Li X, Zhang X, Kang R, Tang D (2016) Identification of ACSL4 as a biomarker and contributor of ferroptosis. Biochem Biophys Res Commun 478:1338–1343

    Article  CAS  PubMed  Google Scholar 

  • Zhang L, Hu R, Li M, Li F, Meng H, Zhu G, Lin J, Feng H (2013) Deferoxamine attenuates iron-induced long-term neurotoxicity in rats with traumatic brain injury. Neurol Sci 34:639–645

    Article  PubMed  Google Scholar 

  • Zhang ZH, Wu QY, Zheng R, Chen C, Chen Y, Liu Q, Hoffmann PR, Ni JZ, Song GL (2017) Selenomethionine mitigates cognitive decline by targeting both Tau hyperphosphorylation and autophagic clearance in an Alzheimer’s disease mouse model. J Neurosci 37:2449–2462

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang YH, Wang DW, Xu SF, Zhang S, Fan YG, Yang YY, Guo SQ, Wang S, Guo T, Wang ZY, Guo C (2018a) 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

    Article  CAS  PubMed  Google Scholar 

  • Zhang Z, Wu Y, Yuan S, Zhang P, Zhang J, Li H, Li X, Shen H, Wang Z, Chen G (2018b) Glutathione peroxidase 4 participates in secondary brain injury through mediating ferroptosis in a rat model of intracerebral hemorrhage. Brain Res 1701:112–125

    Article  CAS  PubMed  Google Scholar 

  • Zille M, Karuppagounder SS, Chen Y, Gough PJ, Bertin J, Finger J, Milner TA, Jonas EA, Ratan RR (2017) Neuronal death after hemorrhagic stroke in vitro and in vivo shares features of ferroptosis and necroptosis. Stroke 48:1033–1043

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

J. Wan was supported by the American Heart Association (Postdoctoral Fellowship Award 18POST33970007); J. Wang was supported by the National Institutes of Health (R21 NS102899), the American Heart Association (Grant-in-Aid 17GRNT33660766), and a Stimulating and Advancing ACCM Research (StAAR) grant from the Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University.

Author information

Authors and Affiliations

  1. Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jieru Wan, Xiuli Yang & Jian Wang

Authors
  1. Jieru Wan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiuli Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jian Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jian Wang .

Editor information

Editors and Affiliations

  1. Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA

    Daolin Tang

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Wan, J., Yang, X., Wang, J. (2019). Ferroptosis in Nervous System Diseases. In: Tang, D. (eds) Ferroptosis in Health and Disease. Springer, Cham. https://doi.org/10.1007/978-3-030-26780-3_10

Download citation

Publish with us

Policies and ethics

Search

Navigation