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Role of iron in neurodegenerative diseases

  • Neurology and Preclinical Neurological Studies - Review Article
  • Published:
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Abstract

Currently, we still lack effective measures to modify disease progression in neurodegenerative diseases. Iron-containing proteins play an essential role in many fundamental biological processes in the central nervous system. In addition, iron is a redox-active ion and can induce oxidative stress in the cell. Although the causes and pathology hallmarks of different neurodegenerative diseases vary, iron dyshomeostasis, oxidative stress and mitochondrial injury constitute a common pathway to cell death in several neurodegenerative diseases. MRI is capable of depicting iron content in the brain, and serves as a potential biomarker for early and differential diagnosis, tracking disease progression and evaluating the effectiveness of neuroprotective therapy. Iron chelators have shown their efficacy against neurodegeneration in a series of animal models, and been applied in several clinical trials. In this review, we summarize recent developments on iron dyshomeostasis in Parkinson’s disease, Alzheimer’s disease, Friedreich ataxia, and Huntington’s disease.

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References

  • Adlard PA, Cherny RA, Finkelstein DI, Gautier E, Robb E, Cortes M, Volitakis I, Liu X, Smith JP, Perez K, Laughton K, Li QX, Charman SA, Nicolazzo JA, Wilkins S, Deleva K, Lynch T, Kok G, Ritchie CW, Tanzi RE, Cappai R, Masters CL, Barnham KJ, Bush AI (2008) Rapid restoration of cognition in Alzheimer’s transgenic mice with 8-hydroxy quinoline analogs is associated with decreased interstitial Abeta. Neuron 59(1):43–55. doi:10.1016/j.neuron.2008.06.018

    Article  CAS  PubMed  Google Scholar 

  • Apple AC, Possin KL, Satris G, Johnson E, Lupo JM, Jakary A, Wong K, Kelley DA, Kang GA, Sha SJ, Kramer JH, Geschwind MD, Nelson SJ, Hess CP (2014) Quantitative 7T phase imaging in premanifest Huntington disease. AJNR Am J Neuroradiol 35(9):1707–1713. doi:10.3174/ajnr.A3932

    Article  CAS  PubMed  PubMed Central  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(4):554–559. doi:10.1002/ana.23817

    Article  CAS  PubMed  Google Scholar 

  • Babcock M, de Silva D, Oaks R, Davis-Kaplan S, Jiralerspong S, Montermini L, Pandolfo M, Kaplan J (1997) Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of frataxin. Science 276(5319):1709–1712

    Article  CAS  PubMed  Google Scholar 

  • Bar-Am O, Amit T, Kupershmidt L, Aluf Y, Mechlovich D, Kabha H, Danovitch L, Zurawski VR, Youdim MB, Weinreb O (2015) Neuroprotective and neurorestorative activities of a novel iron chelator-brain selective monoamine oxidase-A/monoamine oxidase-B inhibitor in animal models of Parkinson’s disease and aging. Neurobiol Aging 36(3):1529–1542. doi:10.1016/j.neurobiolaging.2014.10.026

    Article  CAS  PubMed  Google Scholar 

  • Bartzokis G, Cummings J, Perlman S, Hance DB, Mintz J (1999) Increased basal ganglia iron levels in Huntington disease. Arch Neurol 56(5):569–574

    Article  CAS  PubMed  Google Scholar 

  • Bartzokis G, Lu PH, Tishler TA, Fong SM, Oluwadara B, Finn JP, Huang D, Bordelon Y, Mintz J, Perlman S (2007) Myelin breakdown and iron changes in Huntington’s disease: pathogenesis and treatment implications. Neurochem Res 32(10):1655–1664. doi:10.1007/s11064-007-9352-7

    Article  CAS  PubMed  Google Scholar 

  • 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(10):2288–2301. doi:10.1016/j.neurobiolaging.2014.04.019

    Article  CAS  PubMed  Google Scholar 

  • Becker G, Seufert J, Bogdahn U, Reichmann H, Reiners K (1995) Degeneration of substantia nigra in chronic Parkinson’s disease visualized by transcranial color-coded real-time sonography. Neurology 45(1):182–184

    Article  CAS  PubMed  Google Scholar 

  • Behnke S, Double KL, Duma S, Broe GA, Guenther V, Becker G, Halliday GM (2007) Substantia nigra echomorphology in the healthy very old: correlation with motor slowing. Neuroimage 34(3):1054–1059. doi:10.1016/j.neuroimage.2006.10.010

    Article  CAS  PubMed  Google Scholar 

  • Beinert H, Holm RH, Munck E (1997) Iron-sulfur clusters: nature’s modular, multipurpose structures. Science 277(5326):653–659

    Article  CAS  PubMed  Google Scholar 

  • Berg D (2011) Hyperechogenicity of the substantia nigra: pitfalls in assessment and specificity for Parkinson’s disease. J Neural Trans 118(3):453–461. doi:10.1007/s00702-010-0469-5

    Article  CAS  Google Scholar 

  • Berg D, Siefker C, Becker G (2001) Echogenicity of the substantia nigra in Parkinson’s disease and its relation to clinical findings. J Neurol 248(8):684–689

    Article  CAS  PubMed  Google Scholar 

  • Blazejewska AI, Schwarz ST, Pitiot A, Stephenson MC, Lowe J, Bajaj N, Bowtell RW, Auer DP, Gowland PA (2013) Visualization of nigrosome 1 and its loss in PD: pathoanatomical correlation and in vivo 7 T MRI. Neurology 81(6):534–540. doi:10.1212/WNL.0b013e31829e6fd2

    Article  PubMed  PubMed Central  Google Scholar 

  • Bodovitz S, Falduto MT, Frail DE, Klein WL (1995) Iron levels modulate alpha-secretase cleavage of amyloid precursor protein. J Neurochem 64(1):307–315

    Article  CAS  PubMed  Google Scholar 

  • Boelmans K, Holst B, Hackius M, Finsterbusch J, Gerloff C, Fiehler J, Munchau A (2012) Brain iron deposition fingerprints in Parkinson’s disease and progressive supranuclear palsy. Mov Disord 27(3):421–427. doi:10.1002/mds.24926

    Article  PubMed  Google Scholar 

  • Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM (2007) Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement 3(3):186–191. doi:10.1016/j.jalz.2007.04.381

    Article  PubMed  Google Scholar 

  • Bulteau AL, O’Neill HA, Kennedy MC, Ikeda-Saito M, Isaya G, Szweda LI (2004) Frataxin acts as an iron chaperone protein to modulate mitochondrial aconitase activity. Science 305(5681):242–245. doi:10.1126/science.1098991

    Article  CAS  PubMed  Google Scholar 

  • Cabantchik ZI (2014) Labile iron in cells and body fluids: physiology, pathology, and pharmacology. Front Pharmacol 5:45. doi:10.3389/fphar.2014.00045

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Carroll CB, Zeissler ML, Chadborn N, Gibson K, Williams G, Zajicek JP, Morrison KE, Hanemann CO (2011) Changes in iron-regulatory gene expression occur in human cell culture models of Parkinson’s disease. Neurochem Int 59(1):73–80. doi:10.1016/j.neuint.2011.05.006

    Article  CAS  PubMed  Google Scholar 

  • Castellani RJ, Moreira PI, Perry G, Zhu X (2012) The role of iron as a mediator of oxidative stress in Alzheimer disease. BioFactors 38(2):133–138. doi:10.1002/biof.1010

    Article  CAS  PubMed  Google Scholar 

  • Catala A (2009) Lipid peroxidation of membrane phospholipids generates hydroxy-alkenals and oxidized phospholipids active in physiological and/or pathological conditions. Chem Phys Lipids 157(1):1–11. doi:10.1016/j.chemphyslip.2008.09.004

    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(10):e77023. doi:10.1371/journal.pone.0077023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Connor JR, Menzies SL, St Martin SM, Mufson EJ (1992) A histochemical study of iron, transferrin, and ferritin in Alzheimer’s diseased brains. J Neurosci Res 31(1):75–83. doi:10.1002/jnr.490310111

    Article  CAS  PubMed  Google Scholar 

  • Connor JR, Tucker P, Johnson M, Snyder B (1993) Ceruloplasmin levels in the human superior temporal gyrus in aging and Alzheimer’s disease. Neurosci Lett 159(1–2):88–90

    Article  CAS  PubMed  Google Scholar 

  • Connor JR, Boeshore KL, Benkovic SA, Menzies SL (1994) Isoforms of ferritin have a specific cellular distribution in the brain. J Neurosci Res 37(4):461–465. doi:10.1002/jnr.490370405

    Article  CAS  PubMed  Google Scholar 

  • Connor JR, Snyder BS, Arosio P, Loeffler DA, LeWitt P (1995) A quantitative analysis of isoferritins in select regions of aged, parkinsonian, and Alzheimer’s diseased brains. J Neurochem 65(2):717–724

    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(8753):1304–1308

    Article  CAS  PubMed  Google Scholar 

  • Crespo AC, Silva B, Marques L, Marcelino E, Maruta C, Costa S, Timoteo A, Vilares A, Couto FS, Faustino P, Correia AP, Verdelho A, Porto G, Guerreiro M, Herrero A, Costa C, de Mendonca A, Costa L, Martins M (2014) Genetic and biochemical markers in patients with Alzheimer’s disease support a concerted systemic iron homeostasis dysregulation. Neurobiol Aging 35(4):777–785. doi:10.1016/j.neurobiolaging.2013.10.078

    Article  CAS  PubMed  Google Scholar 

  • Crichton RR, Dexter DT, Ward RJ (2011) Brain iron metabolism and its perturbation in neurological diseases. J Neural Transm 118(3):301–314. doi:10.1007/s00702-010-0470-z

    Article  CAS  PubMed  Google Scholar 

  • Davies P, Moualla D, Brown DR (2011) Alpha-synuclein is a cellular ferrireductase. PLoS ONE 6(1):e15814. doi:10.1371/journal.pone.0015814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Domenico I, Ward DM, di Patti MC, Jeong SY, David S, Musci G, Kaplan J (2007) Ferroxidase activity is required for the stability of cell surface ferroportin in cells expressing GPI-ceruloplasmin. EMBO J 26(12):2823–2831. doi:10.1038/sj.emboj.7601735

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Deibel MA, Ehmann WD, Markesbery WR (1996) Copper, iron, and zinc imbalances in severely degenerated brain regions in Alzheimer’s disease: possible relation to oxidative stress. J Neurol Sci 143(1–2):137–142

    Article  CAS  PubMed  Google Scholar 

  • Devi L, Raghavendran V, Prabhu BM, Avadhani NG, Anandatheerthavarada HK (2008) Mitochondrial import and accumulation of alpha-synuclein impair complex I in human dopaminergic neuronal cultures and Parkinson disease brain. J Biol Chem 283(14):9089–9100. doi:10.1074/jbc.M710012200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Devos D, Moreau C, Devedjian JC, Kluza J, Petrault M, Laloux C, Jonneaux A, Ryckewaert G, Garcon G, Rouaix N, Duhamel A, Jissendi P, Dujardin K, Auger F, Ravasi L, Hopes L, Grolez G, Firdaus W, Sablonniere B, Strubi-Vuillaume I, Zahr N, Destee A, Corvol JC, Poltl D, Leist M, Rose C, Defebvre L, Marchetti P, Cabantchik ZI, Bordet R (2014) Targeting chelatable iron as a therapeutic modality in Parkinson’s disease. Antioxid Redox Signal 21(2):195–210. doi:10.1089/ars.2013.5593

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dexter DT, Wells FR, Lees AJ, Agid F, Agid Y, Jenner P, Marsden CD (1989) Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson’s disease. J Neurochem 52(6):1830–1836

    Article  CAS  PubMed  Google Scholar 

  • Dexter DT, Carayon A, Vidailhet M, Ruberg M, Agid F, Agid Y, Lees AJ, Wells FR, Jenner P, Marsden CD (1990) Decreased ferritin levels in brain in Parkinson’s disease. J Neurochem 55(1):16–20

    Article  CAS  PubMed  Google Scholar 

  • Dexter DT, Statton SA, Whitmore C, Freinbichler W, Weinberger P, Tipton KF, Della Corte L, Ward RJ, Crichton RR (2011) Clinically available iron chelators induce neuroprotection in the 6-OHDA model of Parkinson’s disease after peripheral administration. J Neural Trans 118(2):223–231. doi:10.1007/s00702-010-0531-3

    Article  CAS  Google Scholar 

  • Dexter DT, Martin-Bastida A, Kabba C, Piccini P, Sharp D, Ward R, Newbold R (2014) A pilot 6 months efficacy and safety study utilising the iron chelator deferiprone in early stage Parkinson’s disease [abstract]. Mov Disord 29(Suppl 1):633

    Google Scholar 

  • Dominguez DJ, Ng AC, Poudel G, Stout JC, Churchyard A, Chua P, Egan GF, Georgiou-Karistianis N (2015) Iron accumulation in the basal ganglia in Huntington’s disease: cross-sectional data from the IMAGE-HD study. J Neurol Neurosurg Psychiatry. doi:10.1136/jnnp-2014-310183

    Google Scholar 

  • Doody RS, Thomas RG, Farlow M, Iwatsubo T, Vellas B, Joffe S, Kieburtz K, Raman R, Sun X, Aisen PS, Siemers E, Liu-Seifert H, Mohs R, Alzheimer’s Disease Cooperative Study Steering C, Solanezumab Study G (2014) Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease. N Engl J Med 370(4):311–321. doi:10.1056/NEJMoa1312889

    Article  CAS  PubMed  Google Scholar 

  • Dorsey ER, Constantinescu R, Thompson JP, Biglan KM, Holloway RG, Kieburtz K, Marshall FJ, Ravina BM, Schifitto G, Siderowf A, Tanner CM (2007) Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology 68(5):384–386. doi:10.1212/01.wnl.0000247740.47667.03

    Article  CAS  PubMed  Google Scholar 

  • Everett J, Cespedes E, Shelford LR, Exley C, Collingwood JF, Dobson J, van der Laan G, Jenkins CA, Arenholz E, Telling ND (2014) Ferrous iron formation following the co-aggregation of ferric iron and the Alzheimer’s disease peptide beta-amyloid (1–42). J R Soc Interface 11(95):20140165. doi:10.1098/rsif.2014.0165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Faucheux BA, Martin ME, Beaumont C, Hunot S, Hauw JJ, Agid Y, Hirsch EC (2002) Lack of up-regulation of ferritin is associated with sustained iron regulatory protein-1 binding activity in the substantia nigra of patients with Parkinson’s disease. J Neurochem 83(2):320–330

    Article  CAS  PubMed  Google Scholar 

  • Firdaus WJ, Wyttenbach A, Giuliano P, Kretz-Remy C, Currie RW, Arrigo AP (2006) Huntingtin inclusion bodies are iron-dependent centers of oxidative events. FEBS J 273(23):5428–5441. doi:10.1111/j.1742-4658.2006.05537.x

    Article  CAS  PubMed  Google Scholar 

  • Funke C, Schneider SA, Berg D, Kell DB (2013) Genetics and iron in the systems biology of Parkinson’s disease and some related disorders. Neurochem Int 62(5):637–652. doi:10.1016/j.neuint.2012.11.015

    Article  CAS  PubMed  Google Scholar 

  • Geppert M, Hohnholt MC, Nurnberger S, Dringen R (2012) Ferritin up-regulation and transient ROS production in cultured brain astrocytes after loading with iron oxide nanoparticles. Acta Biomater 8(10):3832–3839. doi:10.1016/j.actbio.2012.06.029

    Article  CAS  PubMed  Google Scholar 

  • Gille G, Reichmann H (2011) Iron-dependent functions of mitochondria—relation to neurodegeneration. J Neural Transm 118(3):349–359. doi:10.1007/s00702-010-0503-7

    Article  CAS  PubMed  Google Scholar 

  • Goetz CG (2010) New developments in depression, anxiety, compulsiveness, and hallucinations in Parkinson’s disease. Mov Disord 25(Suppl 1):S104–S109. doi:10.1002/mds.22636

    Article  PubMed  Google Scholar 

  • Golts N, Snyder H, Frasier M, Theisler C, Choi P, Wolozin B (2002) Magnesium inhibits spontaneous and iron-induced aggregation of alpha-synuclein. J Biol Chem 277(18):16116–16123. doi:10.1074/jbc.M107866200

    Article  CAS  PubMed  Google Scholar 

  • Good PF, Perl DP, Bierer LM, Schmeidler J (1992) Selective accumulation of aluminum and iron in the neurofibrillary tangles of Alzheimer’s disease: a laser microprobe (LAMMA) study. Ann Neurol 31(3):286–292. doi:10.1002/ana.410310310

    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, Cabantchik IZ, Devos D (2015) Ceruloplasmin activity and iron chelation treatment of patients with Parkinson’s disease. BMC Neurol 15:74. doi:10.1186/s12883-015-0331-3

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Grossi C, Francese S, Casini A, Rosi MC, Luccarini I, Fiorentini A, Gabbiani C, Messori L, Moneti G, Casamenti F (2009) Clioquinol decreases amyloid-beta burden and reduces working memory impairment in a transgenic mouse model of Alzheimer’s disease. J Alzheimers Dis 17(2):423–440. doi:10.3233/JAD-2009-1063

    CAS  PubMed  Google Scholar 

  • Guerreiro C, Silva B, Crespo AC, Marques L, Costa S, Timoteo A, Marcelino E, Maruta C, Vilares A, Matos M, Couto FS, Faustino P, Verdelho A, Guerreiro M, Herrero A, Costa C, de Mendonca A, Martins M, Costa L (2015) Decrease in APP and CP mRNA expression supports impairment of iron export in Alzheimer’s disease patients. Biochim Biophys Acta 1852(10 Pt A):2116–2122. doi:10.1016/j.bbadis.2015.07.017

    Article  CAS  PubMed  Google Scholar 

  • Guo C, Wang P, Zhong ML, Wang T, Huang XS, Li JY, Wang ZY (2013a) Deferoxamine inhibits iron induced hippocampal tau phosphorylation in the Alzheimer transgenic mouse brain. Neurochem Int 62(2):165–172. doi:10.1016/j.neuint.2012.12.005

    Article  CAS  PubMed  Google Scholar 

  • Guo C, Wang T, Zheng W, Shan ZY, Teng WP, Wang ZY (2013b) Intranasal deferoxamine reverses iron-induced memory deficits and inhibits amyloidogenic APP processing in a transgenic mouse model of Alzheimer’s disease. Neurobiol Aging 34(2):562–575. doi:10.1016/j.neurobiolaging.2012.05.009

    Article  CAS  PubMed  Google Scholar 

  • Haehner A, Hummel T, Hummel C, Sommer U, Junghanns S, Reichmann H (2007) Olfactory loss may be a first sign of idiopathic Parkinson’s disease. Mov Disord 22(6):839–842. doi:10.1002/mds.21413

    Article  PubMed  Google Scholar 

  • Hansen TM, Nielsen H, Bernth N, Moos T (1999) Expression of ferritin protein and subunit mRNAs in normal and iron deficient rat brain. Brain Res Mol Brain Res 65(2):186–197

    Article  CAS  PubMed  Google Scholar 

  • Hare DJ, Lei P, Ayton S, Roberts BR, Grimm R, George JL, Bishop DP, Beavis AD, Donovan SJ, McColl G, Volitakis I, Masters CL, Adlard PA, Cherny RA, Bush AI, Finkelstein DI, Doble PA (2014) An iron-dopamine index predicts risk of parkinsonian neurodegeneration in the substantia nigra pars compacta. Chem Sci 5(6):2160–2169. doi:10.1039/c3sc53461h

    Article  CAS  Google Scholar 

  • He N, Ling H, Ding B, Huang J, Zhang Y, Zhang Z, Liu C, Chen K, Yan F (2015) Region-specific disturbed iron distribution in early idiopathic Parkinson’s disease measured by quantitative susceptibility mapping. Hum Brain Mapp. doi:10.1002/hbm.22928

    PubMed Central  Google Scholar 

  • Heinemann IU, Jahn M, Jahn D (2008) The biochemistry of heme biosynthesis. Arch Biochem Biophys 474(2):238–251. doi:10.1016/j.abb.2008.02.015

    Article  CAS  PubMed  Google Scholar 

  • Hilditch-Maguire P, Trettel F, Passani LA, Auerbach A, Persichetti F, MacDonald ME (2000) Huntingtin: an iron-regulated protein essential for normal nuclear and perinuclear organelles. Hum Mol Genet 9(19):2789–2797

    Article  CAS  PubMed  Google Scholar 

  • Hoepken HH, Korten T, Robinson SR, Dringen R (2004) Iron accumulation, iron-mediated toxicity and altered levels of ferritin and transferrin receptor in cultured astrocytes during incubation with ferric ammonium citrate. J Neurochem 88(5):1194–1202

    Article  CAS  PubMed  Google Scholar 

  • Jenner P, Dexter DT, Sian J, Schapira AH, Marsden CD (1992) Oxidative stress as a cause of nigral cell death in Parkinson’s disease and incidental Lewy body disease. The Royal Kings and Queens Parkinson’s Disease Research Group. Ann Neurol 32(Suppl):S82–S87

    Article  CAS  PubMed  Google Scholar 

  • Jiang H, Song N, Xu H, Zhang S, Wang J, Xie J (2010) Up-regulation of divalent metal transporter 1 in 6-hydroxydopamine intoxication is IRE/IRP dependent. Cell Res 20(3):345–356. doi:10.1038/cr.2010.20

    Article  CAS  PubMed  Google Scholar 

  • Jin L, Wang J, Zhao L, Jin H, Fei G, Zhang Y, Zeng M, Zhong C (2011) Decreased serum ceruloplasmin levels characteristically aggravate nigral iron deposition in Parkinson’s disease. Brain 134(Pt 1):50–58. doi:10.1093/brain/awq319

    Article  PubMed  Google Scholar 

  • Kaur D, Yantiri F, Rajagopalan S, Kumar J, Mo JQ, Boonplueang R, Viswanath V, Jacobs R, Yang L, Beal MF, DiMonte D, Volitaskis I, Ellerby L, Cherny RA, Bush AI, Andersen JK (2003) Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson’s disease. Neuron 37(6):899–909

    Article  CAS  PubMed  Google Scholar 

  • Kehrer JP (2000) The Haber–Weiss reaction and mechanisms of toxicity. Toxicology 149(1):43–50

    Article  CAS  PubMed  Google Scholar 

  • Keyer K, Imlay JA (1996) Superoxide accelerates DNA damage by elevating free-iron levels. Proc Natl Acad Sci USA 93(24):13635–13640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klausner RD, Rouault TA, Harford JB (1993) Regulating the fate of mRNA: the control of cellular iron metabolism. Cell 72(1):19–28

    Article  CAS  PubMed  Google Scholar 

  • Koeppen AH, Morral JA, Davis AN, Qian J, Petrocine SV, Knutson MD, Gibson WM, Cusack MJ, Li D (2009) The dorsal root ganglion in Friedreich’s ataxia. Acta Neuropathol 118(6):763–776. doi:10.1007/s00401-009-0589-x

    Article  PubMed  Google Scholar 

  • Koeppen AH, Ramirez RL, Yu D, Collins SE, Qian J, Parsons PJ, Yang KX, Chen Z, Mazurkiewicz JE, Feustel PJ (2012) Friedreich’s ataxia causes redistribution of iron, copper, and zinc in the dentate nucleus. Cerebellum 11(4):845–860. doi:10.1007/s12311-012-0383-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koeppen AH, Kuntzsch EC, Bjork ST, Ramirez RL, Mazurkiewicz JE, Feustel PJ (2013) Friedreich ataxia: metal dysmetabolism in dorsal root ganglia. Acta Neuropathol Commun 1:26. doi:10.1186/2051-5960-1-26

    Article  PubMed  PubMed Central  Google Scholar 

  • Kupershmidt L, Weinreb O, Amit T, Mandel S, Bar-Am O, Youdim MB (2011) Novel molecular targets of the neuroprotective/neurorescue multimodal iron chelating drug M30 in the mouse brain. Neuroscience 189:345–358. doi:10.1016/j.neuroscience.2011.03.040

    Article  CAS  PubMed  Google Scholar 

  • Kwon DH, Kim JM, Oh SH, Jeong HJ, Park SY, Oh ES, Chi JG, Kim YB, Jeon BS, Cho ZH (2012) Seven-Tesla magnetic resonance images of the substantia nigra in Parkinson disease. Ann Neurol 71(2):267–277. doi:10.1002/ana.22592

    Article  PubMed  Google Scholar 

  • Lane DJ, Merlot AM, Huang ML, Bae DH, Jansson PJ, Sahni S, Kalinowski DS, Richardson DR (2015) Cellular iron uptake, trafficking and metabolism: key molecules and mechanisms and their roles in disease. Biochim Biophys Acta 1853(5):1130–1144. doi:10.1016/j.bbamcr.2015.01.021

    Article  CAS  PubMed  Google Scholar 

  • Lehericy S, Bardinet E, Poupon C, Vidailhet M, Francois C (2014) 7 Tesla magnetic resonance imaging: a closer look at substantia nigra anatomy in Parkinson’s disease. Mov Disord 29(13):1574–1581. doi:10.1002/mds.26043

    Article  CAS  PubMed  Google Scholar 

  • Leidgens S, Bullough KZ, Shi H, Li F, Shakoury-Elizeh M, Yabe T, Subramanian P, Hsu E, Natarajan N, Nandal A, Stemmler TL, Philpott CC (2013) Each member of the poly-r(C)-binding protein 1 (PCBP) family exhibits iron chaperone activity toward ferritin. J Biol Chem 288(24):17791–17802. doi:10.1074/jbc.M113.460253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leitner DF, Connor JR (2012) Functional roles of transferrin in the brain. Biochim Biophys Acta 1820(3):393–402. doi:10.1016/j.bbagen.2011.10.016

    Article  CAS  PubMed  Google Scholar 

  • Li DH, Zhang LY, Hu YY, Jiang XF, Zhou HY, Yang Q, Kang WY, Liu J, Chen SD (2015) Transcranial sonography of the substantia nigra and its correlation with DAT-SPECT in the diagnosis of Parkinson’s disease. Parkinsonism Relat Disord 21(8):923–928. doi:10.1016/j.parkreldis.2015.05.024

    Article  PubMed  Google Scholar 

  • Lill R, Dutkiewicz R, Elsasser HP, Hausmann A, Netz DJ, Pierik AJ, Stehling O, Urzica E, Muhlenhoff U (2006) Mechanisms of iron-sulfur protein maturation in mitochondria, cytosol and nucleus of eukaryotes. Biochim Biophys Acta 1763(7):652–667. doi:10.1016/j.bbamcr.2006.05.011

    Article  CAS  PubMed  Google Scholar 

  • Lin CI, Gollub EG, Beattie DS (1982) Synthesis of the proteins of complex III of the mitochondrial respiratory chain in heme-deficient cells. Eur J Biochem 128(2–3):309–313

    CAS  PubMed  Google Scholar 

  • Macerollo A, Perry R, Stamelou M, Batla A, Mazumder AA, Adams ME, Bhatia KP (2014) Susceptibility-weighted imaging changes suggesting brain iron accumulation in Huntington’s disease: an epiphenomenon which causes diagnostic difficulty. Eur J Neurol 21(2):e16–e17. doi:10.1111/ene.12298

    Article  CAS  PubMed  Google Scholar 

  • Mangialasche F, Solomon A, Winblad B, Mecocci P, Kivipelto M (2010) Alzheimer’s disease: clinical trials and drug development. Lancet Neurol 9(7):702–716. doi:10.1016/S1474-4422(10)70119-8

    Article  CAS  PubMed  Google Scholar 

  • Martelli A, Puccio H (2014) Dysregulation of cellular iron metabolism in Friedreich ataxia: from primary iron-sulfur cluster deficit to mitochondrial iron accumulation. Front Pharmacol 5:130. doi:10.3389/fphar.2014.00130

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Martin WR, Wieler M, Gee M (2008) Midbrain iron content in early Parkinson disease: a potential biomarker of disease status. Neurology 70(16 Pt 2):1411–1417. doi:10.1212/01.wnl.0000286384.31050.b5

    Article  CAS  PubMed  Google Scholar 

  • Mastroberardino PG, Hoffman EK, Horowitz MP, Betarbet R, Taylor G, Cheng D, Anderson M (2009) A novel transferrin/TfR2-mediated mitochondrial iron transport system is disrupted in Parkinson's disease. Neurobiol dis 34(3):417–431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mena NP, Urrutia PJ, Lourido F, Carrasco CM, Nunez MT (2015) Mitochondrial iron homeostasis and its dysfunctions in neurodegenerative disorders. Mitochondrion 21:92–105. doi:10.1016/j.mito.2015.02.001

    Article  CAS  PubMed  Google Scholar 

  • Michaeli S, Oz G, Sorce DJ, Garwood M, Ugurbil K, Majestic S, Tuite P (2007) Assessment of brain iron and neuronal integrity in patients with Parkinson’s disease using novel MRI contrasts. Mov Disord 22(3):334–340. doi:10.1002/mds.21227

    Article  PubMed  Google Scholar 

  • Miyamoto M, Miyamoto T (2013) Neuroimaging of rapid eye movement sleep behavior disorder: transcranial ultrasound, single-photon emission computed tomography, and positron emission tomography scan data. Sleep Med 14(8):739–743. doi:10.1016/j.sleep.2013.03.004

    Article  PubMed  Google Scholar 

  • Moos T (1996) Immunohistochemical localization of intraneuronal transferrin receptor immunoreactivity in the adult mouse central nervous system. J Comp Neurol 375(4):675–692. doi:10.1002/(SICI)1096-9861(19961125)375:4<675:AID-CNE8>3.0.CO;2-Z

    Article  CAS  PubMed  Google Scholar 

  • Moos T, Morgan EH (2004) The significance of the mutated divalent metal transporter (DMT1) on iron transport into the Belgrade rat brain. J Neurochem 88(1):233–245

    Article  CAS  PubMed  Google Scholar 

  • Moos T, Rosengren Nielsen T (2006) Ferroportin in the postnatal rat brain: implications for axonal transport and neuronal export of iron. Semin Pediatr Neurol 13(3):149–157. doi:10.1016/j.spen.2006.08.003

    Article  PubMed  Google Scholar 

  • Moos T, Oates PS, Morgan EH (1998) Expression of the neuronal transferrin receptor is age dependent and susceptible to iron deficiency. J Comp Neurol 398(3):420–430

    Article  CAS  PubMed  Google Scholar 

  • Moos T, Skjoerringe T, Gosk S, Morgan EH (2006) Brain capillary endothelial cells mediate iron transport into the brain by segregating iron from transferrin without the involvement of divalent metal transporter 1. J Neurochem 98(6):1946–1958. doi:10.1111/j.1471-4159.2006.04023.x

    Article  CAS  PubMed  Google Scholar 

  • Muller M, Leavitt BR (2014) Iron dysregulation in Huntington’s disease. J Neurochem 130(3):328–350. doi:10.1111/jnc.12739

    Article  CAS  PubMed  Google Scholar 

  • Munch G, Luth HJ, Wong A, Arendt T, Hirsch E, Ravid R, Riederer P (2000) Crosslinking of alpha-synuclein by advanced glycation endproducts—an early pathophysiological step in Lewy body formation? J Chem Neuroanat 20(3–4):253–257

    Article  CAS  PubMed  Google Scholar 

  • Nilsson R, Schultz IJ, Pierce EL, Soltis KA, Naranuntarat A, Ward DM, Baughman JM, Paradkar PN, Kingsley PD, Culotta VC, Kaplan J, Palis J, Paw BH, Mootha VK (2009) Discovery of genes essential for heme biosynthesis through large-scale gene expression analysis. Cell Metab 10(2):119–130. doi:10.1016/j.cmet.2009.06.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ortega R, Carmona A, Roudeau S, Perrin L, Ducic T, Carboni E, Bohic S, Cloetens P, Lingor P (2015) Alpha-synuclein over-expression induces increased iron accumulation and redistribution in iron-exposed neurons. Mol Neurobiol. doi:10.1007/s12035-015-9146-x

    PubMed  Google Scholar 

  • Ostrerova-Golts N, Petrucelli L, Hardy J, Lee JM, Farer M, Wolozin B (2000) The A53T alpha-synuclein mutation increases iron-dependent aggregation and toxicity. J Neurosci 20(16):6048–6054

    CAS  PubMed  Google Scholar 

  • Pandolfo M, Arpa J, Delatycki MB, Le Quan Sang KH, Mariotti C, Munnich A, Sanz-Gallego I, Tai G, Tarnopolsky MA, Taroni F, Spino M, Tricta F (2014) Deferiprone in Friedreich ataxia: a 6-month randomized controlled trial. Ann Neurol 76(4):509–521. doi:10.1002/ana.24248

    Article  CAS  PubMed  Google Scholar 

  • Parker WD Jr, Parks J, Filley CM, Kleinschmidt-DeMasters BK (1994) Electron transport chain defects in Alzheimer’s disease brain. Neurology 44(6):1090–1096

    Article  PubMed  Google Scholar 

  • Pelizzoni I, Zacchetti D, Campanella A, Grohovaz F, Codazzi F (2013) Iron uptake in quiescent and inflammation-activated astrocytes: a potentially neuroprotective control of iron burden. Biochim Biophys Acta 1832(8):1326–1333. doi:10.1016/j.bbadis.2013.04.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pyatigorskaya N, Sharman M, Corvol JC, Valabregue R, Yahia-Cherif L, Poupon F, Cormier-Dequaire F, Siebner H, Klebe S, Vidailhet M, Brice A, Lehericy S (2015) High nigral iron deposition in LRRK2 and Parkin mutation carriers using R2* relaxometry. Mov Disord 30(8):1077–1084. doi:10.1002/mds.26218

    Article  CAS  PubMed  Google Scholar 

  • Raha AA, Vaishnav RA, Friedland RP, Bomford A, Raha-Chowdhury R (2013) The systemic iron-regulatory proteins hepcidin and ferroportin are reduced in the brain in Alzheimer’s disease. Acta Neuropathol Commun 1:55. doi:10.1186/2051-5960-1-55

    Article  PubMed  PubMed Central  Google Scholar 

  • Rathore KI, Redensek A, David S (2012) Iron homeostasis in astrocytes and microglia is differentially regulated by TNF-alpha and TGF-beta1. Glia 60(5):738–750. doi:10.1002/glia.22303

    Article  PubMed  Google Scholar 

  • Riederer P, Sofic E, Rausch WD, Schmidt B, Reynolds GP, Jellinger K, Youdim MB (1989) Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains. J Neurochem 52(2):515–520

    Article  CAS  PubMed  Google Scholar 

  • Rogers JT, Randall JD, Cahill CM, Eder PS, Huang X, Gunshin H, Leiter L, McPhee J, Sarang SS, Utsuki T, Greig NH, Lahiri DK, Tanzi RE, Bush AI, Giordano T, Gullans SR (2002) An iron-responsive element type II in the 5′-untranslated region of the Alzheimer’s amyloid precursor protein transcript. J Biol Chem 277(47):45518–45528. doi:10.1074/jbc.M207435200

    Article  CAS  PubMed  Google Scholar 

  • Rossi M, Ruottinen H, Soimakallio S, Elovaara I, Dastidar P (2013) Clinical MRI for iron detection in Parkinson’s disease. Clin Imaging 37(4):631–636. doi:10.1016/j.clinimag.2013.02.001

    Article  PubMed  Google Scholar 

  • Rotig A, de Lonlay P, Chretien D, Foury F, Koenig M, Sidi D, Munnich A, Rustin P (1997) Aconitase and mitochondrial iron-sulphur protein deficiency in Friedreich ataxia. Nat Genet 17(2):215–217. doi:10.1038/ng1097-215

    Article  CAS  PubMed  Google Scholar 

  • Rouault TA (2006) The role of iron regulatory proteins in mammalian iron homeostasis and disease. Nat Chem Biol 2(8):406–414. doi:10.1038/nchembio807

    Article  CAS  PubMed  Google Scholar 

  • Salazar J, Mena N, Hunot S, Prigent A, Alvarez-Fischer D, Arredondo M, Duyckaerts C, Sazdovitch V, Zhao L, Garrick LM, Nunez MT, Garrick MD, Raisman-Vozari R, Hirsch EC (2008) Divalent metal transporter 1 (DMT1) contributes to neurodegeneration in animal models of Parkinson’s disease. Proc Natl Acad Sci USA 105(47):18578–18583. doi:10.1073/pnas.0804373105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salkovic-Petrisic M, Knezovic A, Osmanovic-Barilar J, Smailovic U, Trkulja V, Riederer P, Amit T, Mandel S, Youdim MB (2015) Multi-target iron-chelators improve memory loss in a rat model of sporadic Alzheimer’s disease. Life Sci. doi:10.1016/j.lfs.2015.06.026

    PubMed  Google Scholar 

  • Salloway S, Sperling R, Fox NC, Blennow K, Klunk W, Raskind M, Sabbagh M, Honig LS, Porsteinsson AP, Ferris S, Reichert M, Ketter N, Nejadnik B, Guenzler V, Miloslavsky M, Wang D, Lu Y, Lull J, Tudor IC, Liu E, Grundman M, Yuen E, Black R, Brashear HR, Bapineuzumab, Clinical Trial I (2014) Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med 370(4):322–333. doi:10.1056/NEJMoa1304839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sanchez-Castaneda C, Squitieri F, Di Paola M, Dayan M, Petrollini M, Sabatini U (2015) The role of iron in gray matter degeneration in Huntington’s disease: a magnetic resonance imaging study. Hum Brain Mapp 36(1):50–66. doi:10.1002/hbm.22612

    Article  PubMed  Google Scholar 

  • Sayre LM, Perry G, Harris PL, Liu Y, Schubert KA, Smith MA (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(1):270–279

    Article  CAS  PubMed  Google Scholar 

  • Shachar DB, Kahana N, Kampel V, Warshawsky A, Youdim MB (2004) Neuroprotection by a novel brain permeable iron chelator, VK-28, against 6-hydroxydopamine lession in rats. Neuropharmacology 46(2):254–263

    Article  PubMed  CAS  Google Scholar 

  • Shokolenko I, Venediktova N, Bochkareva A, Wilson GL, Alexeyev MF (2009) Oxidative stress induces degradation of mitochondrial DNA. Nucleic Acids Res 37(8):2539–2548. doi:10.1093/nar/gkp100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Silvestri L, Camaschella C (2008) A potential pathogenetic role of iron in Alzheimer’s disease. J Cell Mol Med 12(5A):1548–1550. doi:10.1111/j.1582-4934.2008.00356.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Silvestri L, Pagani A, Camaschella C (2008) Furin-mediated release of soluble hemojuvelin: a new link between hypoxia and iron homeostasis. Blood 111(2):924–931. doi:10.1182/blood-2007-07-100677

    Article  CAS  PubMed  Google Scholar 

  • Skjorringe T, Burkhart A, Johnsen KB, Moos T (2015) Divalent metal transporter 1 (DMT1) in the brain: implications for a role in iron transport at the blood-brain barrier, and neuronal and glial pathology. Front Mol Neurosci 8:19. doi:10.3389/fnmol.2015.00019

    PubMed  PubMed Central  Google Scholar 

  • Smith MA, Hirai K, Hsiao K, Pappolla MA, Harris PL, Siedlak SL, Tabaton M, Perry G (1998) Amyloid-beta deposition in Alzheimer transgenic mice is associated with oxidative stress. J Neurochem 70(5):2212–2215

    Article  CAS  PubMed  Google Scholar 

  • Song N, Wang J, Jiang H, Xie J (2010) Ferroportin 1 but not hephaestin contributes to iron accumulation in a cell model of Parkinson’s disease. Free Radic Biol Med 48(2):332–341. doi:10.1016/j.freeradbiomed.2009.11.004

    Article  CAS  PubMed  Google Scholar 

  • Stadtman ER (2006) Protein oxidation and aging. Free Radic Res 40(12):1250–1258. doi:10.1080/10715760600918142

    Article  CAS  PubMed  Google Scholar 

  • Todorich B, Zhang X, Slagle-Webb B, Seaman WE, Connor JR (2008) Tim-2 is the receptor for H-ferritin on oligodendrocytes. J Neurochem 107(6):1495–1505. doi:10.1111/j.1471-4159.2008.05678.x

    Article  CAS  PubMed  Google Scholar 

  • Tsai CF, Wu RM, Huang YW, Chen LL, Yip PK, Jeng JS (2007) Transcranial color-coded sonography helps differentiation between idiopathic Parkinson’s disease and vascular parkinsonism. J Neurol 254(4):501–507. doi:10.1007/s00415-006-0403-9

    Article  PubMed  Google Scholar 

  • Urrutia PJ, Mena NP, Nunez MT (2014) The interplay between iron accumulation, mitochondrial dysfunction, and inflammation during the execution step of neurodegenerative disorders. Front Pharmacol 5:38. doi:10.3389/fphar.2014.00038

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • van Rooden S, Doan NT, Versluis MJ, Goos JD, Webb AG, Oleksik AM, van der Flier WM, Scheltens P, Barkhof F, Weverling-Rynsburger AW, Blauw GJ, Reiber JH, van Buchem MA, Milles J, van der Grond J (2015) 7T T(2)*-weighted magnetic resonance imaging reveals cortical phase differences between early- and late-onset Alzheimer’s disease. Neurobiol Aging 36(1):20–26. doi:10.1016/j.neurobiolaging.2014.07.006

    Article  PubMed  Google Scholar 

  • Visser CC, Voorwinden LH, Crommelin DJ, Danhof M, de Boer AG (2004) Characterization and modulation of the transferrin receptor on brain capillary endothelial cells. Pharm Res 21(5):761–769

    Article  CAS  PubMed  Google Scholar 

  • Wan L, Nie G, Zhang J, Luo Y, Zhang P, Zhang Z, Zhao B (2011) beta-Amyloid peptide increases levels of iron content and oxidative stress in human cell and Caenorhabditis elegans models of Alzheimer disease. Free Radic Biol Med 50(1):122–129. doi:10.1016/j.freeradbiomed.2010.10.707

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Su B, Siedlak SL, Moreira PI, Fujioka H, Wang Y, Casadesus G, Zhu X (2008) Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins. Proc Natl Acad Sci USA 105(49):19318–19323. doi:10.1073/pnas.0804871105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ward RJ, Zucca FA, Duyn JH, Crichton RR, Zecca L (2014) The role of iron in brain ageing and neurodegenerative disorders. Lancet Neurol 13(10):1045–1060. doi:10.1016/S1474-4422(14)70117-6

    Article  CAS  PubMed  Google Scholar 

  • Wardman P, Candeias LP (1996) Fenton chemistry: an introduction. Radiat Res 145(5):523–531

    Article  CAS  PubMed  Google Scholar 

  • Wieler M, Gee M, Martin WR (2015) Longitudinal midbrain changes in early Parkinson’s disease: iron content estimated from R2*/MRI. Parkinsonism Relat Disord 21(3):179–183. doi:10.1016/j.parkreldis.2014.11.017

    Article  PubMed  Google Scholar 

  • Wong BX, Duce JA (2014) The iron regulatory capability of the major protein participants in prevalent neurodegenerative disorders. Front Pharmacol 5:81. doi:10.3389/fphar.2014.00081

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yamamoto A, Shin RW, Hasegawa K, Naiki H, Sato H, Yoshimasu F, Kitamoto T (2002) Iron(III) induces aggregation of hyperphosphorylated τ and its reduction to iron(II) reverses the aggregation: implications in the formation of neurofibrillary tangles of Alzheimer’s disease. J Neurochem 82(5):1137–1147

    Article  CAS  PubMed  Google Scholar 

  • Zecca L, Gallorini M, Schunemann V, Trautwein AX, Gerlach M, Riederer P, Vezzoni P, Tampellini D (2001) Iron, neuromelanin and ferritin content in the substantia nigra of normal subjects at different ages: consequences for iron storage and neurodegenerative processes. J Neurochem 76(6):1766–1773

    Article  CAS  PubMed  Google Scholar 

  • Zecca L, Fariello R, Riederer P, Sulzer D, Gatti A, Tampellini D (2002) The absolute concentration of nigral neuromelanin, assayed by a new sensitive method, increases throughout the life and is dramatically decreased in Parkinson’s disease. FEBS Lett 510(3):216–220

    Article  CAS  PubMed  Google Scholar 

  • Zecca L, Berg D, Arzberger T, Ruprecht P, Rausch WD, Musicco M, Tampellini D, Riederer P, Gerlach M, Becker G (2005) In vivo detection of iron and neuromelanin by transcranial sonography: a new approach for early detection of substantia nigra damage. Mov Disord 20(10):1278–1285. doi:10.1002/mds.20550

    Article  PubMed  Google Scholar 

  • Zeineh MM, Chen Y, Kitzler HH, Hammond R, Vogel H, Rutt BK (2015) Activated iron-containing microglia in the human hippocampus identified by magnetic resonance imaging in Alzheimer disease. Neurobiol Aging 36(9):2483–2500. doi:10.1016/j.neurobiolaging.2015.05.022

    Article  CAS  PubMed  Google Scholar 

  • Zhang Z, Huang L, Shulmeister VM, Chi YI, Kim KK, Hung LW, Crofts AR, Berry EA, Kim SH (1998) Electron transfer by domain movement in cytochrome bc1. Nature 392(6677):677–684. doi:10.1038/33612

    Article  CAS  PubMed  Google Scholar 

  • Zheng W, Xin N, Chi ZH, Zhao BL, Zhang J, Li JY, Wang ZY (2009) Divalent metal transporter 1 is involved in amyloid precursor protein processing and Abeta generation. FASEB J 23(12):4207–4217. doi:10.1096/fj.09-135749

    Article  CAS  PubMed  Google Scholar 

  • Zucca FA, Basso E, Cupaioli FA, Ferrari E, Sulzer D, Casella L, Zecca L (2014) Neuromelanin of the human substantia nigra: an update. Neurotox Res 25(1):13–23. doi:10.1007/s12640-013-9435-y

    Article  CAS  PubMed  Google Scholar 

  • Zucca FA, Segura-Aguilar J, Ferrari E, Munoz P, Paris I, Sulzer D, Sarna T, Casella L, Zecca L (2015) Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson’s disease. Prog Neurobiol. doi:10.1016/j.pneurobio.2015.09.012

    PubMed  Google Scholar 

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  1. Center of Clinical Neuroscience, University Hospital Carl Gustav Carus, Dresden University of Technology, Fetscherstr. 74, 01307, Dresden, Germany

    Kai Li

  2. Department of Neurology, University Hospital Carl Gustav Carus, Dresden University of Technology, Fetscherstr. 74, 01307, Dresden, Germany

    Heinz Reichmann

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Li, K., Reichmann, H. Role of iron in neurodegenerative diseases. J Neural Transm 123, 389–399 (2016). https://doi.org/10.1007/s00702-016-1508-7

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