Iron toxicity in neurodegeneration

BioMetals

Volumn 25, Issue 4, 2012, Pages 761-776

  Núñez, Marco T ^a   Urrutia, Pamela ^a   Mena, Natalia ^a   Aguirre, Pabla ^a   Tapia, Victoria ^a   Salazar, Julio ^a  

^a UNIVERSITY OF CHILE   (Chile)

Author keywords

Fe S clusters; GSH; Iron homeostasis; Mitochondria dysfunction; Neurodegeneration

Indexed keywords

1,2,3,6 TETRAHYDRO 1 METHYL 4 PHENYLPYRIDINE; 6 TRANSMEMBRANE EPITHELIAL ANTIGEN OF THE PROSTATE 3; CHEMOKINE RECEPTOR CXCR4; FERRITIN; GLUTATHIONE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; IRON REGULATORY PROTEIN 1; LIPOPOLYSACCHARIDE; MEMBRANE PROTEIN; N METHYL DEXTRO ASPARTIC ACID; NATURAL RESISTANCE ASSOCIATED MACROPHAGE PROTEIN 2; NEUROMELANIN; PROTEIN FPN1; PROTEIN ZIP14; PROTEIN ZIP14A; PROTEIN ZIP14B; REACTIVE OXYGEN METABOLITE; STROMAL CELL DERIVED RECEPTOR 2; SUCCINATE DEHYDROGENASE; TRANSFERRIN; TRANSFERRIN RECEPTOR; TRANSIENT RECEPTOR POTENTIAL CHANNEL 6; UNCLASSIFIED DRUG; VOLTAGE DEPENDENT ANION CHANNEL;

ALZHEIMER DISEASE; ARTICLE; BINDING AFFINITY; DEGENERATIVE DISEASE; HOMEOSTASIS; HUMAN; HUNTINGTON CHOREA; IMMUNOREACTIVITY; IRON ABSORPTION; IRON OVERLOAD; LIPID PEROXIDATION; LOCUS CERULEUS; NERVE DEGENERATION; NONHUMAN; OLIGODENDROGLIA; OXIDATION REDUCTION STATE; OXIDATIVE STRESS; PARKINSON DISEASE; PROTEIN AGGREGATION; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN MODIFICATION; PROTEIN MOTIF; PROTEIN SYNTHESIS; SOLUBILITY; SUBSTANTIA NIGRA; THERMODYNAMICS; UPREGULATION;

ANIMALS; GLUTATHIONE; HOMEOSTASIS; HUMANS; IRON; MODELS, BIOLOGICAL; NEURODEGENERATIVE DISEASES; OXIDATIVE STRESS; THERMODYNAMICS;

EID: 84864917070     PISSN: 09660844     EISSN: 15728773     Source Type: Journal    
DOI: 10.1007/s10534-012-9523-0     Document Type: Article

References (153)

1. Aguirre P, Mena N, Tapia V, Arredondo M, Núñez MT (2005) Iron homeostasis in neuronal cells: a role for IREG1. BMC Neurosci 6:3
2. Barnham KJ, Bush AI (2008) Metals in Alzheimer's and Parkinson's diseases. Curr Opin Chem Biol 12(2):222-228
3. Bartzokis G, Beckson M, Hance DB, Marx P, Foster JA, Marder SR (1997) MR evaluation of age-related increase of brain iron in young adult and older normal males. Magn Reson Imaging 15(1):29-35
4. Bartzokis G, Sultzer D, Cummings J, Holt LE, Hance DB, Henderson VW, Mintz J (2000) In vivo evaluation of brain iron in Alzheimer disease using magnetic resonance imaging. Arch Gen Psychiatry 57(1):47-53
5. Beinert H, Emptage MH, Dreyer JL, Scott RA, Hahn JE, Hodgson KO, Thomson AJ (1983) Iron-sulfur stoichiometry and structure of iron-sulfur clusters in three-iron proteins: evidence for [3Fe-4S] clusters. Proc Natl Acad Sci USA 80(2):393-396
6. Berg D, Youdim MB (2006) Role of iron in neurodegenerative disorders. Top Magn Reson Imaging 17(1):5-17
7. Boserup MW, Lichota J, Haile D, Moos T (2011) Heterogenous distribution of ferroportin-containing neurons in mouse brain. Biometals 24(2):357-375
8. Braak H, Braak E (1991) Neuropathological stageing of Alzheimer- related changes. Acta Neuropathol 82(4):239-259
9. Bradbury MWB (1997) Transport of Iron in the blood-brain- Ccrebrospinal fluid system. J Neurochem 69(2):443-454
10. Brennan WA Jr, Bird ED, Aprille JR (1985) Regional mitochondrial respiratory activity in Huntington's disease brain. J Neurochem 44(6):1948-1950
11. Burdo JR, Menzies SL, Simpson IA, Garrick LM, Garrick MD, Dolan KG, Haile DJ, Beard JL, Connor JR (2001) Distribution of divalent metal transporter 1 and metal transport protein 1 in the normal and Belgrade rat. J Neurosci Res 66(6):1198-1207
12. Cairo G, Recalcati S (2007) Iron-regulatory proteins: molecular biology and pathophysiological implications. Expert Rev Mol Med 9(33):1-13
13. 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(10):1640-1645
14. Chinopoulos C, Adam-Vizi V (2001) Mitochondria deficient in complex I activity are depolarized by hydrogen peroxide in nerve terminals: relevance to Parkinson's disease. J Neurochem 76(1):302-306
15. Chinta SJ, Andersen JK (2006) Reversible inhibition of mitochondrial complex I activity following chronic dopaminergic glutathione depletion in vitro: implications for Parkinson's disease. Free Radic Biol Med 41(9):1442-1448
16. Collingwood JF, Mikhaylova A, Davidson M, Batich C, Streit WJ, Terry J, Dobson J (2005) In situ characterization and mapping of iron compounds in Alzheimer's disease tissue. J Alzheimers Dis 7(4):267-272
17. Collingwood JF, Chong RK, Kasama T, Cervera-Gontard L, Dunin-Borkowski RE, Perry G, Posfai M, Siedlak SL, Simpson ET, Smith MA, Dobson J (2008) Three-dimensional tomographic imaging and characterization of iron compounds within Alzheimer's plaque core material. J Alzheimers Dis 14(2):235-245
18. Connor JR, Benkovic SA (1992) Iron regulation in the brain: histochemical, biochemical, and molecular considerations. Ann Neurol 32(Suppl):S51-S61
19. Connor JR, Snyder BS, Beard JL, Fine RE, Mufson EJ (1992) Regional distribution of iron and iron-regulatory proteins in the brain in aging and Alzheimer's disease. J Neurosci Res 31(2):327-335
20. Cozzi A, Santambrogio P, Corsi B, Campanella A, Arosio P, Levi S (2006) Characterization of the l-ferritin variant 460InsA responsible of a hereditary ferritinopathy disorder. Neurobiol Dis 23(3):644-652
21. Curtis AR, Fey C, Morris CM, Bindoff LA, Ince PG, Chinnery PF, Coulthard A, Jackson MJ, Jackson AP, McHale DP, Hay D, Barker WA, Markham AF, Bates D, Curtis A, Burn J (2001) Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease. Nat Genet 28(4):350-354
22. Davis DG, Schmitt FA, Wekstein DR, Markesbery WR (1999) Alzheimer neuropathologic alterations in aged cognitively normal subjects. J Neuropathol Exp Neurol 58(4):376-388
23. Davison AN (1987) Pathophysiology of ageing brain. Gerontology 33(3-4):129-135
24. De Domenico I, Vaughn MB, Li L, Bagley D, Musci G, Ward DM, Kaplan J (2006) Ferroportin-mediated mobilization of ferritin iron precedes ferritin degradation by the proteasome. EMBO J 25(22):5396-5404
25. Devalia V, Carter K, Walker AP, Perkins SJ, Worwood M, May A, Dooley JS (2002) Autosomal dominant reticuloendothelial iron overload associated with a 3-base pair deletion in the ferroportin 1 gene (SLC11A3). Blood 100(2):695-697
26. Dexter DT, Carayon A, Javoy-Agid F, Agid Y, Wells FR, Daniel SE, Lees AJ, Jenner P, Marsden CD (1991) Alterations in the levels of iron, ferritin and other trace metals in Parkinson's disease and other neurodegenerative diseases affecting the basal ganglia. Brain 114(Pt 4):1953-1975
27. Ding B, Chen KM, Ling HW, Sun F, Li X, Wan T, Chai WM, Zhang H, Zhan Y, Guan YJ (2009) Correlation of iron in the hippocampus with MMSE in patients with Alzheimer's disease. J Magn Reson Imaging 29(4):793-798
28. Double KL, Gerlach M, Schunemann V, Trautwein AX, Zecca L, Gallorini M, Youdim MB, Riederer P, Ben-Shachar D (2003) Iron-binding characteristics of neuromelanin of the human substantia nigra. Biochem Pharmacol 66(3):489-494
29. Dringen R, Gutterer JM, Hirrlinger J (2000) Glutathione metabolism in brain metabolic interaction between astrocytes and neurons in the defense against reactive oxygen species. Eur J Biochem 267(16):4912-4916
30. Duyckaerts C (2004) Looking for the link between plaques and tangles. Neurobiol Aging 25(6):735-739 (discussion 743-736)
31. Duyckaerts C, Delatour B, Potier MC (2009) Classification and basic pathology of Alzheimer disease. Acta Neuropathol 118(1):5-36
32. Epsztejn S, Kakhlon O, Glickstein H, Breuer W, Cabantchik I (1997) Fluorescence analysis of the labile iron pool of mammalian cells. Anal Biochem 248(1):31-40
33. Falangola MF, Lee SP, Nixon RA, Duff K, Helpern JA (2005) Histological co-localization of iron in Abeta plaques of PS/ APP transgenic mice. Neurochem Res 30(2):201-205
34. 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
35. Fisher J, Devraj K, Ingram J, Slagle-Webb B, Madhankumar AB, Liu X, Klinger M, Simpson IA, Connor JR (2007) Ferritin: a novel mechanism for delivery of iron to the brain and other organs. Am J Physiol Cell Physiol 293(2):C641-C649
36. Gaasch JA, Geldenhuys WJ, Lockman PR, Allen DD, Van der Schyf CJ (2007) Voltage-gated calcium channels provide an alternate route for iron uptake in neuronal cell cultures. Neurochem Res 32(10):1686-1693
37. Garrick MD, Garrick LM (2009) Cellular iron transport. Biochim Biophys Acta 1790(5):309-325
38. Gerlach M, Riederer P, Double KL (2008) Neuromelanin-bound ferric iron as an experimental model of dopaminergic neurodegeneration in Parkinson's disease. Parkinsonism Relat Disord 14(Suppl 2):S185-S188
39. Giampa C, DeMarch Z, Patassini S, Bernardi G, Fusco FR (2007) Immunohistochemical localization of TRPC6 in the rat substantia nigra. Neurosci Lett 424(3):170-174
40. Girijashanker K, He L, Soleimani M, Reed JM, Li H, Liu Z, Wang B, Dalton TP, Nebert DW (2008) Slc39a14 gene encodes ZIP14, a metal/bicarbonate symporter: similarities to the ZIP8 transporter. Mol Pharmacol 73(5):1413-1423
41. Glickstein H, El RB, Link G, Breuer W, Konijn AM, Hershko C, Nick H, Cabantchik ZI (2006) Action of chelators in ironloaded cardiac cells: accessibility to intracellular labile iron and functional consequences. Blood 108(9):3195-3203
42. Gómez FJ, Aguirre P, Gonzalez-Billault C, Núñez MT (2011)Iron mediates neuritic tree collapse in mesencephalic neurons treated with 1-methyl-4-phenylpyridinium (MPP?). J Neural Transm 118(3):421-431
43. Gorell JM, Ordidge RJ, Brown GG, Deniau JC, Buderer NM, Helpern JA (1995) Increased iron-related MRI contrast in the substantia nigra in Parkinson's disease. Neurology 45(6):1138-1143
44. Graf E, Mahoney JR, Bryant RG, Eaton JW (1984) Iron-catalyzed hydroxyl radical formation. Stringent requirement for free iron coordination site. J Biol Chem 259(6):3620-3624
45. Griffiths PD, Dobson BR, Jones GR, Clarke DT (1999) Iron in the basal ganglia in Parkinson's disease. An in vitro study using extended X-ray absorption fine structure and cryoelectron microscopy. Brain 122(Pt 4):667-673
46. Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, Nussberger S, Gollan JL, Hediger MA (1997) Cloning and characterization of a mammalian protoncoupled metal-ion transporter. Nature 388(6641):482-488
47. Haeger P, Alvarez A, Leal N, Adasme T, Núñez MT, Hidalgo C (2010) Increased hippocampal expression of the divalent metal transporter 1 (DMT1) mRNA variants 1B and ?IRE and DMT1 protein after NMDA-receptor stimulation or spatial memory training. Neurotoxic Res 17(3):238-247
48. Harrison PM, Arosio P (1996) The ferritins: molecular properties, iron storage function and cellular regulation. Biochim Biophys Acta 1275(3):161-203
49. Hidalgo C, Núñez MT (2007) Calcium, iron and neuronal function. IUBMB Life 59(4-5):280-285
50. Hirsch EC, Brandel JP, Galle P, Javoy-Agid F, Agid Y (1991) Iron and aluminum increase in the substantia nigra of patients with Parkinson's disease: an X-ray microanalysis. J Neurochem 56(2):446-451
51. Hubert N, Hentze MW (2002) Previously uncharacterized isoforms of divalent metal transporter (DMT)-1: implications for regulation and cellular function. Proc Natl Acad Sci USA 99(19):12345-12350
52. Itagaki S, McGeer PL, Akiyama H, Zhu S, Selkoe D (1989) Relationship of microglia and astrocytes to amyloid deposits of Alzheimer disease. J Neuroimmunol 24(3): 173-182
53. Jack CR Jr, Wengenack TM, Reyes DA, Garwood M, Curran GL, Borowski BJ, Lin J, Preboske GM, Holasek SS, Adriany G, Poduslo JF (2005) In vivo magnetic resonance microimaging of individual amyloid plaques in Alzheimer's transgenic mice. J Neurosci 25(43):10041-10048
54. Jefferies WA, Food MR, Gabathuler R, Rothenberger S, Yamada T, Yasuhara O, McGeer PL (1996) Reactive microglia specifically associated with amyloid plaques in Alzheimer's disease brain tissue express melanotransferrin. Brain Res 712(1):122-126
55. Jellinger KA (1999) The role of iron in neurodegeneration: prospects for pharmacotherapy of Parkinson's disease. Drugs Aging 14(2):115-140
56. Johnstone M, Gearing AJ, Miller KM (1999) A central role for astrocytes in the inflammatory response to beta-amyloid; chemokines, cytokines and reactive oxygen species are produced. J Neuroimmunol 93(1-2):182-193
57. Joseph JA, Shukitt-Hale B, Casadesus G, Fisher D (2005) Oxidative stress and inflammation in brain aging: nutritional considerations. Neurochem Res 30(6-7):927-935
58. Kakhlon O, Cabantchik ZI (2002) The labile iron pool: characterization, measurement, and participation in cellular processes(1). Free Radic Biol Med 33(8):1037-1046
59. Kastner A, Hirsch EC, Lejeune O, Javoy-Agid F, Rascol O, Agid Y (1992) Is the vulnerability of neurons in the substantia nigra of patients with Parkinson's disease related to their neuromelanin content? J Neurochem 59(3):1080-1089
60. 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
61. Kaur D, Lee D, Ragapolan S, Andersen JK (2009) Glutathione depletion in immortalized midbrain-derived dopaminergic neurons results in increases in the labile iron pool: implications for Parkinson's disease. Free Radic Biol Med 46(5):593-598
62. Knutson MD, Vafa MR, Haile DJ, Wessling-Resnick M (2003) Iron loading and erythrophagocytosis increase ferroportin 1 (FPN1) expression in J774 macrophages. Blood 102(12): 4191-4197
63. Krizaj D (2005) Compartmentalization of calcium entry pathways in mouse rods. Eur J Neurosci 22(12):3292-3296
64. Kruszewski M (2003) Labile iron pool: the main determinant of cellular response to oxidative stress. Mutat Res 531(1-2): 81-92
65. 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
66. LaFerla FM, Green KN, Oddo S (2007) Intracellular amyloidbeta in Alzheimer's disease. Nat Rev Neurosci 8(7):499-509
67. Langston JW, Ballard P, Tetrud JW, Irwin I (1983) Chronic Parkinsonism in humans due to a product of meperidineanalog synthesis. Science 219(4587):979-980
68. Latunde-Dada GO, Xiang L, Simpson RJ, McKie AT (2011) Duodenal cytochrome b (Cybrd 1) and HIF-2alpha expression during acute hypoxic exposure in mice. Eur J Nutr 50(8):699-704
69. Lichten LA, Cousins RJ (2009) Mammalian zinc transporters: nutritional and physiologic regulation. Annu Rev Nutr 29:153-176
70. Lill R, Muhlenhoff U (2008) Maturation of iron-sulfur proteins in eukaryotes: mechanisms, connected processes, and diseases. Annu Rev Biochem 77:669-700
71. 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
72. Lis A, Paradkar PN, Singleton S, Kuo HC, Garrick MD, Roth JA (2005) Hypoxia induces changes in expression of isoforms of the divalent metal transporter (DMT1) in rat pheochromocytoma (PC12) cells. Biochem Pharmacol 69(11): 1647-1655
73. Liu X, Theil EC (2005) Ferritins: dynamic management of biological iron and oxygen chemistry. Acc Chem Res 38(3):167-175
74. Liuzzi JP, Lichten LA, Rivera S, Blanchard RK, Aydemir TB, Knutson MD, Ganz T, Cousins RJ (2005) Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response. Proc Natl Acad Sci USA 102(19):6843-6848
75. Liuzzi JP, Aydemir F, Nam H, Knutson MD, Cousins RJ (2006) Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells. Proc Natl Acad Sci USA 103(37):13612-13617
76. Lockman JA, Geldenhuys WJ, Bohn KA, Desilva SF, Allen DD, Van der Schyf CJ (2012) Differential effect of nimodipine in attenuating iron-induced toxicity in brain- and bloodbrain barrier-associated cell types. Neurochem Res 37(1): 134-142
77. Lodi R, Cooper JM, Bradley JL, Manners D, Styles P, Taylor DJ, Schapira AH (1999) Deficit of in vivo mitochondrial ATP production in patients with Friedreich ataxia. Proc Natl Acad Sci USA 96(20):11492-11495
78. 2+ channel blockers reverse iron overload by a new mechanism via divalent metal transporter- 1. Nat Med 13(4):448-454
79. Mancuso C, Scapagini G, Curro D, Giuffrida Stella AM, De Marco C, Butterfield DA, Calabrese V (2007) Mitochondrial dysfunction, free radical generation and cellular stress response in neurodegenerative disorders. Front Biosci 12:1107-1123
80. Markesbery WR, Lovell MA (1998) Four-hydroxynonenal, a product of lipid peroxidation, is increased in the brain in Alzheimer's disease. Neurobiol Aging 19(1):33-36
81. Martelli A, Wattenhofer-Donze M, Schmucker S, Bouvet S, Reutenauer L, Puccio H (2007) Frataxin is essential for extramitochondrial Fe-S cluster proteins in mammalian tissues. Hum Mol Genet 16(22):2651-2658
82. McKie AT, Marciani P, Rolfs A, Brennan K, Wehr K, Barrow D, Miret S, Bomford A, Peters TJ, Farzaneh F, Hediger MA, Hentze MW, Simpson RJ (2000) A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol Cell 5(2):299-309
83. McKie AT, Barrow D, Latunde-Dada GO, Rolfs A, Sager G, Mudaly E, Mudaly M, Richardson C, Barlow D, Bomford A, Peters TJ, Raja KB, Shirali S, Hediger MA, Farzaneh F, Simpson RJ (2001) An iron-regulated ferric reductase associated with the absorption of dietary iron. Science 291(5509):1755-1759
84. Meda L, Baron P, Scarlato G (2001) Glial activation in Alzheimer's disease: the role of Abeta and its associated proteins. Neurobiol Aging 22(6):885-893
85. Mehlhase J, Sandig G, Pantopoulos K, Grune T (2005) Oxidation- induced ferritin turnover in microglial cells: role of proteasome. Free Radic Biol Med 38(2):276-285
86. Meister A, Anderson ME (1983) Glutathione. Annu Rev Biochem 52:711-760
87. Mena NP, Bulteau AL, Salazar J, Hirsch EC, Núñez MT (2011) Effect of mitochondrial complex I inhibition on Fe-S cluster protein activity. Biochem Biophys Res Commun 409(2):241-246
88. Moos T, Morgan EH (1998) Evidence for low molecular weight, non-transferrin-bound iron in rat brain and cerebrospinal fluid. J Neurosci Res 54(4):486-494
89. 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
90. Moos T, Rosengren Nielsen T, Skjorringe T, Morgan EH (2007) Iron trafficking inside the brain. J Neurochem 103(5): 1730-1740
91. Mura C, Delgado R, Aguirre P, Bacigalupo J, Nuñez MT (2006) SHSY5Y neuroblastoma cells survival to iron challenge results in a quiescent and functional cell population. J Neurochem 98(1):11-19
92. Mwanjewe J, Grover AK (2004) Role of transient receptor potential canonical 6 (TRPC6) in non-transferrin-bound iron uptake in neuronal phenotype PC12 cells. Biochem J 378(Pt 3):975-982
93. Núñez MT, Gallardo V, Muñoz P, Tapia V, Esparza A, Salazar J, Speisky H (2004) Progressive iron accumulation induces a biphasic change in the glutathione content of neuroblastoma cells. Free Radic Biol Med 37(7):953-960
94. Ohgami RS, Campagna DR, Greer EL, Antiochos B, McDonald A, Chen J, Sharp JJ, Fujiwara Y, Barker JE, Fleming MD (2005) Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. Nat Genet 37(11):1264-1269
95. Ohgami RS, Campagna DR, McDonald A, Fleming MD (2006) The Steap proteins are metalloreductases. Blood 108(4): 1388-1394
96. 2+ channels in iron transport and ironoverload cardiomyopathy. J Mol Med (Berl) 84(5):349-364
97. Paradkar PN, Roth JA (2006) Post-translational and transcriptional regulation of DMT1 during P19 embryonic carcinoma cell differentiation by retinoic acid. Biochem J 394(Pt 1):173-183
98. 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
99. Pelizzoni I, Macco R, Morini MF, Zacchetti D, Grohovaz F, Codazzi F (2011) Iron handling in hippocampal neurons: activity-dependent iron entry and mitochondria-mediated neurotoxicity. Aging Cell 10(1):172-183
100. Perry TL, Godin DV, Hansen S (1982) Parkinson's disease: a disorder due to nigral glutathione deficiency? Neurosci Lett 33(3):305-310
101. Perry G, Taddeo MA, Petersen RB, Castellani RJ, Harris PL, Siedlak SL, Cash AD, Liu Q, Nunomura A, Atwood CS, Smith MA (2003) Adventiously-bound redox active iron and copper are at the center of oxidative damage in Alzheimer disease. Biometals 16(1):77-81
102. Qian ZM, Wu XM, Fan M, Yang L, Du F, Yung WH, Ke Y (2011) Divalent metal transporter 1 is a hypoxia-inducible gene. J Cell Physiol 226(6):1596-1603
103. Quintana C, Bellefqih S, Laval JY, Guerquin-Kern JL, Wu TD, Avila J, Ferrer I, Arranz R, Patino C (2006) Study of the localization of iron, ferritin, and hemosiderin in Alzheimer's disease hippocampus by analytical microscopy at the subcellular level. J Struct Biol 153(1):42-54
104. Ramirez G, Rey S, von Bernhardi R (2008) Proinflammatory stimuli are needed for induction of microglial cell-mediated AbetaPP{244-C} and Abeta-neurotoxicity in hippocampal cultures. J Alzheimers Dis 15(1):45-59
105. Reynolds MR, Berry RW, Binder LI (2007) Nitration in neurodegeneration: deciphering the ''Hows'' ''nYs''. Biochemistry 46(25):7325-7336
106. Rouault TA, Zhang DL, Jeong SY (2009) Brain iron homeostasis, the choroid plexus, and localization of iron transport proteins. Metab Brain Dis 24(4):673-684
107. Salazar J, Mena N, Hunot S, Prigent A, Alvarez-Fischer D, Arredondo M, Duyckaerts C, Sazdovitch V, Zhao L, Garrick LM, Núñez 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
108. Salgado JC, Olivera-Nappa A, Gerdtzen ZP, Tapia V, Theil EC, Conca C, Núñez MT (2010) Mathematical modeling of the dynamic storage of iron in ferritin. BMC Syst Biol 4:147
109. Sayre LM, Perry G, Atwood CS, Smith MA (2000) The role of metals in neurodegenerative diseases. Cell Mol Biol (Noisy-le-grand) 46(4):731-741
110. Schafer FQ, Buettner GR (2001) Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med 30(11): 1191-1212
111. Schapira AH (2006) Mitochondrial disease. Lancet 368(9529): 70-82
112. Schapira AH, Gegg M (2011) Mitochondrial contribution to Parkinson's disease pathogenesis. Parkinsons Dis 2011: 159160
113. Schapira AH, Cooper JM, Dexter D, Clark JB, Jenner P, Marsden CD (1990) Mitochondrial complex I deficiency in Parkinson's disease. J Neurochem 54(3):823-827
114. Shachar DB, Kahana N, Kampel V, Warshawsky A, Youdim MB (2004) Neuroprotection by a novel brain permeable iron chelator, VK-28, against 6-hydroxydopamine lesion in rats. Neuropharmacology 46(2):254-263
115. Shaw GC, Cope JJ, Li L, Corson K, Hersey C, Ackermann GE, Gwynn B, Lambert AJ, Wingert RA, Traver D, Trede NS, Barut BA, Zhou Y, Minet E, Donovan A, Brownlie A, Balzan R, Weiss MJ, Peters LL, Kaplan J, Zon LI, Paw BH (2006) Mitoferrin is essential for erythroid iron assimilation. Nature 440(7080):96-100
116. Sheftel A, Stehling O, Lill R (2010) Iron-sulfur proteins in health and disease. Trends Endocrinol Metab 21(5):302-314
117. Shi Q, Gibson GE (2007) Oxidative stress and transcriptional regulation in Alzheimer disease. Alzheimer Dis Assoc Disord 21(4):276-291
118. 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(3):348-355
119. Sienko MJ, Plane RA (1976) Chemistry, 5th edn. McGraw-Hill, New York
120. Snyder AM, Connor JR (2009) Iron, the substantia nigra and related neurological disorders. Biochim Biophys Acta 1790(7):606-614
121. Sofic E, Riederer P, Heinsen H, Beckmann H, Reynolds GP, Hebenstreit G, Youdim MB (1988) Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain. J Neural Transm 74(3):199-205
122. 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
123. Spiro TG, Salman P (1974) Inorganic chemistry. In: Jacobs A, Worwood M (eds) Iron in biochemistry and medicine. Academic Press, New York, pp 1-28
124. Symons MCR, Gutteridge JMC (1998) Free radicals and iron: chemistry, biology, and medicine. Oxford University Press, Oxford
125. Thompson KJ, Shoham S, Connor JR (2001) Iron and neurodegenerative disorders. Brain Res Bull 55(2):155-164
126. Todorich B, Zhang X, Connor JR (2011) H-ferritin is the major source of iron for oligodendrocytes. Glia 59(6):927-935
127. Tulpule K, Robinson SR, Bishop GM, Dringen R (2010) Uptake of ferrous iron by cultured rat astrocytes. J Neurosci Res 88(3):563-571
128. Unciuleac M, Warkentin E, Page CC, Boll M, Ermler U (2004) Structure of a xanthine oxidase-related 4-hydroxybenzoyl- CoA reductase with an additional [4Fe-4S] cluster and an inverted electron flow. Structure 12(12):2249-2256
129. Vargas JD, Herpers B, McKie AT, Gledhill S, McDonnell J, van den Heuvel M, Davies KE, Ponting CP (2003) Stromal cell-derived receptor 2 and cytochrome b561 are functional ferric reductases. Biochim Biophys Acta 1651(1-2):116-123
130. Vidal R, Delisle MB, Rascol O, Ghetti B (2003) Hereditary ferritinopathy. J Neurol Sci 207(1-2):110-111
131. von Bernhardi R (2007) Glial cell dysregulation: a new perspective on Alzheimer disease. Neurotoxic Res 12(4):215-232
132. Vymazal J, Righini A, Brooks RA, Canesi M, Mariani C, Leonardi M, Pezzoli G (1999) T1 and T2 in the brain of healthy subjects, patients with Parkinson disease, and patients with multiple system atrophy: relation to iron content. Radiology 211(2):489-495
133. Wallander ML, Leibold EA, Eisenstein RS (2006) Molecular control of vertebrate iron homeostasis by iron regulatory proteins. Biochim Biophys Acta 1763(7):668-689
134. Wang D, Wang LH, Zhao Y, Lu YP, Zhu L (2010) Hypoxia regulates the ferrous iron uptake and reactive oxygen species level via divalent metal transporter 1 (DMT1) Exon1B by hypoxia-inducible factor-1. IUBMB Life 62(8):629-636
135. Weinreb O, Amit T, Mandel S, Youdim MB (2011) Novel therapeutic approach for neurodegenerative pathologies: multitarget iron-chelating drugs regulating hypoxiainducible factor 1 signal transduction pathway. Neurodegener Dis. [Epub ahead of print]
136. Williams K, Wilson MA, Bressler J (2000) Regulation and developmental expression of the divalent metal-ion transporter in the rat brain. Cell Mol Biol (Noisy-le-grand) 46(3):563-571
137. Wilson RB (2006) Iron dysregulation in Friedreich ataxia. Semin Pediatr Neurol 13(3):166-175
138. Wood PM (1988) The potential diagram for oxygen at pH 7. Biochem J 253(1):287-289
139. Wright RO, Baccarelli A (2007) Metals and neurotoxicology. J Nutr 137(12):2809-2813
140. Yamada M (2004) Cerebral amyloid angiopathy and gene polymorphisms. J Neurol Sci 226(1-2):41-44
141. Yang F, Liu XB, Quinones M, Melby PC, Ghio A, Haile DJ (2002) Regulation of reticuloendothelial iron transporter MTP1 (Slc11a3) by inflammation. J Biol Chem 277(42): 39786-39791
142. Yasha TC, Shankar L, Santosh V, Das S, Shankar SK (1997) Histopathological & immunohistochemical evaluation of ageing changes in normal human brain. Indian J Med Res 105:141-150
143. Ye H, Rouault TA (2010) Erythropoiesis and iron sulfur cluster biogenesis. Adv Hematol 2010
144. Youdim MB, Buccafusco JJ (2005) Multi-functional drugs for various CNS targets in the treatment of neurodegenerative disorders. Trends Pharmacol Sci 26(1):27-35
145. Youdim MB, Ben-Shachar D, Riederer P (1989) Is Parkinson's disease a progressive siderosis of substantia nigra resulting in iron and melanin induced neurodegeneration? Acta Neurol Scand Suppl 126:47-54
146. Youdim MB, Stephenson G, Ben-Shachar D (2004) Ironing iron out in Parkinson's disease and other neurodegenerative diseases with iron chelators: a lesson from 6-hydroxydopamine and iron chelators, desferal and VK-28. Ann N Y Acad Sci 1012:306-325
147. Zecca L, Tampellini D, Gatti A, Crippa R, Eisner M, Sulzer D, Ito S, Fariello R, Gallorini M (2002) The neuromelanin of human substantia nigra and its interaction with metals. J Neural Transm 109(5-6):663-672
148. Zecca L, Zucca FA, Wilms H, Sulzer D (2003) Neuromelanin of the substantia nigra: a neuronal black hole with protective and toxic characteristics. Trends Neurosci 26(11):578-580
149. Zecca L, Youdim MB, Riederer P, Connor JR, Crichton RR (2004) Iron, brain ageing and neurodegenerative disorders. Nat Rev Neurosci 5(11):863-873
150. Zhang Y, Marcillat O, Giulivi C, Ernster L, Davies KJ (1990) The oxidative inactivation of mitochondrial electron transport chain components and ATPase. J Biol Chem 265(27):16330-16336
151. Zheng H, Youdim MB, Fridkin M (2010) Site-activated chelators targeting acetylcholinesterase and monoamine oxidase for Alzheimer's therapy. ACS Chem Biol 5(6):603-610
152. Zhu W, Xie W, Pan T, Xu P, Fridkin M, Zheng H, Jankovic J, Youdim MB, Le W (2007) Prevention and restoration of lactacystin-induced nigrostriatal dopamine neuron degeneration by novel brain-permeable iron chelators. FASEB J 21(14):3835-3844
153. Zoccarato F, Toscano P, Alexandre A (2005) Dopamine-derived dopaminochrome promotes H(2)O(2) release at mitochondrial complex I: stimulation by rotenone, control by Ca(2+), and relevance to Parkinson disease. J Biol Chem 280(16):15587-15594