Does cellular iron dysregulation play a causative role in Parkinson's disease?

Ageing Research Reviews

Volumn 3, Issue 3, 2004, Pages 327-343

  Kaur, Deepinder ^a   Andersen, Julie ^a  

^a BUCK INSTITUTE FOR RESEARCH ON AGING   (United States)

Author keywords

Synuclein; Iron; Iron regulatory proteins; Mitochondrial dysfunction; Oxidative stress; Parkinson's disease

Indexed keywords

ALPHA SYNUCLEIN; IRON; IRON REGULATORY FACTOR; IRON REGULATORY PROTEIN 1; IRON REGULATORY PROTEIN 2;

BIOACCUMULATION; BRAIN DEGENERATION; CELL LEVEL; CELL METABOLISM; CHEMICAL ANALYSIS; DISEASE ASSOCIATION; DISORDERS OF MITOCHONDRIAL FUNCTIONS; ENERGY METABOLISM; GENETIC ASSOCIATION; GENETIC CORRELATION; GENETIC RISK; HUMAN; IRON METABOLISM; LEWY BODY; METABOLIC DISORDER; OXIDATIVE STRESS; PARKINSON DISEASE; PARKINSONISM; PATHOPHYSIOLOGY; REGULATORY MECHANISM; REVIEW;

ALPHA-SYNUCLEIN; ANIMALS; HOMEOSTASIS; HUMANS; IRON; IRON REGULATORY PROTEIN 1; IRON REGULATORY PROTEIN 2; IRON-REGULATORY PROTEINS; MESENCEPHALON; MITOCHONDRIA; MODELS, BIOLOGICAL; NERVE TISSUE PROTEINS; NEURODEGENERATIVE DISEASES; OXIDATIVE STRESS; PARKINSON DISEASE; PROTEIN BINDING; SYNUCLEINS;

EID: 3042654997     PISSN: 15681637     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.arr.2004.01.003     Document Type: Review

References (96)

1. Alam Z.I., Jenner A., Daniel S.E., Lees A.J., Cairns N., Marsden C.D., Jenner P., Halliwell B. Oxidative DNA damage in the parkinsonian brain: an apparent selective increase in 8-hydroxyguanine levels in substantia nigra. J. Neurochem. 69:1997;1196-1203
2. Antonini A., Leenders K.L., Meier D., Oertel W.H., Boesiger P., Anliker M. T2 relaxation time in patients with Parkinson's disease. Neurology. 43:1993;697-700
3. Balla G., Jacob H.S., Balla J., Rosenberg M., Nath K., Apple F., Eaton J.W., Vercellotti G.M. Ferritin: a cytoprotective antioxidant strategem of endothelium. J. Biol. Chem. 267:1992;18148-18153
4. Becker G., Seufert J., Bogdahn U., Reichmann H., Reiners K. Degeneration of substantia nigra in chronic Parkinson's disease visualized by transcranial color-coded real-time sonography. Neurology. 45:1995;182-184
5. Ben-Shachar D., Eshel G., Finberg J.P., Youdim M.B. The iron chelator desferrioxamine (Desferal) retards 6-hydroxydopamine-induced degeneration of nigrostriatal dopamine neurons. J. Neurochem. 56:1991;1441-1444
6. Berg D., Jabs B., Merschdorf U., Beckmann H., Becker G. Echogenicity of substantia nigra determined by transcranial ultrasound correlates with severity of parkinsonian symptoms induced by neuroleptic therapy. Biol. Psychiatry. 50:2001;463-467
7. Bernheimer H., Birkmayer W., Hornykiewicz O., Jellinger K., Seitelberger F. Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J. Neurol. Sci. 20:1973;415-455
8. Borie C., Gasparini F., Verpillat P., Bonnet A.M., Agid Y., Hetet G., Brice A., Durr A., Grandchamp B. Association study between iron-related genes polymorphisms and Parkinson's disease. J. Neurol. 249:2002;801-804
9. Braak, H., Braak, E., 2000. Pathoanatomy of Parkinson's disease. J. Neurol. 247 (Suppl. 2) II3-II10.
10. Bradley J.L., Blake J.C., Chamberlain S., Thomas P.K., Cooper J.M., Schapira A.H. Clinical, biochemical and molecular genetic correlations in Friedreich's ataxia. Hum. Mol. Genet. 9:2000;275-282
11. Cairo G., Pietrangelo A. Iron regulatory proteins in pathobiology. Biochem. J. 352(2):2000;241-250
12. Castellani R.J., Siedlak S.L., Perry G., Smith M.A. Sequestration of iron by Lewy bodies in Parkinson's disease. Acta Neuropathol. (Berlin). 100:2000;111-114
13. Castelnau P.A., Garrett R.S., Palinski W., Witztum J.L., Campbell I.L., Powell H.C. Abnormal iron deposition associated with lipid peroxidation in transgenic mice expressing interleukin-6 in the brain. J. Neuropathol. Exp. Neurol. 57:1998;268-282
14. Connor J.R., Menzies S.L., Burdo J.R., Boyer P.J. Iron and iron management proteins in neurobiology. Pediatr. Neurol. 25:2001;118-129
15. Crompton D.E., Chinnery P.F., Fey C., Curtis A.R., Morris C.M., Kierstan J., Burt A., Young F., Coulthard A., Curtis A., Ince P.G., Bates D., Jackson M.J., Burn J. Neuroferritinopathy: a window on the role of iron in neurodegeneration. Blood Cells Mol. Dis. 29:2002;522-531
16. Curtis A.R., Fey C., Morris C.M., Bindoff L.A., Ince P.G., Chinnery P.F., Coulthard A., Jackson M.J., Jackson A.P., McHale D.P., Hay D., Barker W.A., Markham A.F., Bates D., Curtis A., Burn J. Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease. Nat. Genet. 28:2001;350-354
17. de Silva H.R., Khan N.L., Wood N.W. The genetics of Parkinson's disease. Curr. Opin. Genet. Dev. 10:2000;292-298
18. Dexter D.T., Wells F.R., Lees A.J., Agid F., Agid Y., Jenner P., Marsden C.D. Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson's disease. J. Neurochem. 52:1989;1830-1836
19. Drayer B.P., Olanow W., Burger P., Johnson G.A., Herfkens R., Riederer S. Parkinson plus syndrome: diagnosis using high field MR imaging of brain iron. Radiology. 159:1986;493-498
20. Duda J.E., Lee V.M., Trojanowski J.Q. Neuropathology of synuclein aggregates. J. Neurosci. Res. 61:2000a;121-127
21. Duda J.E., Giasson B.I., Gur T.L., Montine T.J., Robertson D., Biaggioni I., Hurtig H.I., Stern M.B., Gollomp S.M., Grossman M., Lee V.M., Trojanowski J.Q. Immunohistochemical and biochemical studies demonstrate a distinct profile of alpha-synuclein permutations in multiple system atrophy. J. Neuropathol. Exp. Neurol. 59:2000b;830-841
22. Earle K.M. Studies on Parkinson's disease including X-ray fluorescent spectroscopy of formalin fixed brain tissue. J. Neuropathol. Exp. Neurol. 27:1968;1-14
23. Eisenstein R.S. Iron regulatory proteins and the molecular control of mammalian iron metabolism. Annu. Rev. Nutr. 20:2000;627-662
24. Elbaz A., Grigoletto F., Baldereschi M., Breteler M.M., Manubens-Bertran J.M., Lopez-Pousa S., Dartigues J.F., Alperovitch A., Tzourio C., Rocca W.A. Familial aggregation of Parkinson's disease: a population-based case-control study in Europe. EUROPARKINSON Study Group. Neurology. 52:1999;1876-1882
25. Epsztejn S., Glickstein H., Picard V., Slotki I.N., Breuer W., Beaumont C., Cabantchik Z.I. H-ferritin subunit overexpression in erythroid cells reduces the oxidative stress response and induces multidrug resistance properties. Blood. 94:1999;3593-3603
26. Fahn S. Description of Parkinson's disease as a clinical syndrome. Ann. N. Y. Acad. Sci. 991:2003;1-14
27. Faucheux B.A., Martin M.E., Beaumont C., Hunot S., Hauw J.J., Agid Y., Hirsch E.C. 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. 83:2002;320-330
28. Ferreira C., Santambrogio P., Martin M.E., Andrieu V., Feldmann G., Henin D., Beaumont C. H ferritin knockout mice: a model of hyperferritinemia in the absence of iron overload. Blood. 98:2001;525-532
29. Fredriksson A., Schroder N., Eriksson P., Izquierdo I., Archer T. Neonatal iron potentiates adult MPTP-induced neurodegenerative and functional deficits. Parkinsonism Relat. Disord. 7:2001;97-105
30. Galazka-Friedman J., Friedman A. Controversies about iron in parkinsonian and control substantia nigra. Acta Neurobiol. Exp. (Wars). 57:1997;217-225
31. Giasson B.I., Duda J.E., Murray I.V., Chen Q., Souza J.M., Hurtig H.I., Ischiropoulos H., Trojanowski J.Q., Lee V.M. Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. Science. 290:2000;985-989
32. Glinka Y., Tipton K.F., Youdim M.B. Nature of inhibition of mitochondrial respiratory complex I by 6-hydroxydopamine. J. Neurochem. 66:1996;2004-2010
33. Griffiths P.D., Crossman A.R. Distribution of iron in the basal ganglia and neocortex in postmortem tissue in Parkinson's disease and Alzheimer's disease. Dementia. 4:1993;61-65
34. Griffiths P.D., Dobson B.R., Jones G.R., Clarke D.T. Iron in the basal ganglia in Parkinson's disease. An in vitro study using extended X-ray absorption fine structure and cryo-electron microscopy. Brain. 122(4):1999;667-673
35. Grunblatt E., Mandel S., Berkuzki T., Youdim M.B. Apomorphine protects against MPTP-induced neurotoxicity in mice. Mov. Disord. 14:1999;612-618
36. Hall S., Rutledge J.N., Schallert T. MRI, brain iron and experimental Parkinson's disease. J. Neurol. Sci. 113:1992;198-208
37. Hashimoto M., Hsu L.J., Xia Y., Takeda A., Sisk A., Sundsmo M., Masliah E. Oxidative stress induces amyloid-like aggregate formation of NACP/alpha-synuclein in vitro. Neuroreport. 10:1999;717-721
38. He Y., Thong P.S., Lee T., Leong S.K., Mao B.Y., Dong F., Watt F. Dopaminergic cell death precedes iron elevation in MPTP-injected monkeys. Free Radic. Biol. Med. 35:2003;540-547
39. Hentze M.W., Kuhn L.C. Molecular control of vertebrate iron metabolism: mRNA-based regulatory circuits operated by iron, nitric oxide, and oxidative stress. Proc. Natl. Acad. Sci. U.S.A. 93:1996;8175-8182
40. Hsu L.J., Sagara Y., Arroyo A., Rockenstein E., Sisk A., Mallory M., Wong J., Takenouchi T., Hashimoto M., Masliah E. Alpha-synuclein promotes mitochondrial deficit and oxidative stress. Am. J. Pathol. 157:2000;401-410
41. Jellinger K., Paulus W., Grundke-Iqbal I., Riederer P., Youdim M.B. Brain iron and ferritin in Parkinson's and Alzheimer's diseases. J. Neural Trans. Park. Dis. Dement. Sect. 2:1990;327-340
42. Jenner P. Oxidative stress in Parkinson's disease. Ann. Neurol. 53(Suppl. 3):2003;S26-S36. (discussion S36-S38)
43. Jenner P., Dexter D.T., Sian J., Schapira A.H., Marsden C.D. 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.):1992;S82-S87
44. Kaur D., Yantiri F., Rajagopalan S., Kumar J., Mo J.Q., Boonplueang R., Viswanath V., Jacobs R., Yang L., Beal M.F., DiMonte D., Volitaskis I., Ellerby L., Cherny R.A., Bush A.I., Andersen J.K. Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson's disease. Neuron. 37:2003;899-909
45. Kidd P.M. Parkinson's disease as multifactorial oxidative neurodegeneration: implications for integrative management. Altern. Med. Rev. 5:2000;502-529
46. Kruger R., Kuhn W., Muller T., Woitalla D., Graeber M., Kosel S., Przuntek H., Epplen J.T., Schols L., Riess O. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nat. Genet. 18:1998;106-108
47. Kwak E.L., Larochelle D.A., Beaumont C., Torti S.V., Torti F.M. Role for NF-kappa B in the regulation of ferritin H by tumor necrosis factor-alpha. J. Biol. Chem. 270:1995;15285-15293
48. Lan J., Jiang D.H. Excessive iron accumulation in the brain: a possible potential risk of neurodegeneration in Parkinson's disease. J. Neural Trans. 104:1997a;649-660
49. Lan J., Jiang D.H. Desferrioxamine and vitamin E protect against iron and MPTP-induced neurodegeneration in mice. J. Neural Trans. 104:1997b;469-481
50. Lang A.E., Lozano A.M. Parkinson's disease. Second of two parts. N. Engl. J. Med. 339:1998a;1130-1143
51. Lang A.E., Lozano A.M. Parkinson's disease. First of two parts. N. Engl. J. Med. 339:1998b;1044-1053
52. LaVaute T., Smith S., Cooperman S., Iwai K., Land W., Meyron-Holtz E., Drake S.K., Miller G., Abu-Asab M., Tsokos M., Switzer R. III, Grinberg A., Love P., Tresser N., Rouault T.A. Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice. Nat. Genet. 27:2001;209-214
53. Lehermitte J.K.W., McAlpine M.A. On the occurance of abnormal deposits of iron in the brain in Parkinson's disease with special reference to its location. J. Neurol. Psychopathol. 5:1924;195-208
54. Levites Y., Youdim M.B., Maor G., Mandel S. Attenuation of 6-hydroxydopamine (6-OHDA)-induced nuclear factor-kappaB (NF-kappaB) activation and cell death by tea extracts in neuronal cultures. Biochem. Pharmacol. 63:2002;21-29
55. Lin E., Graziano J.H., Freyer G.A. Regulation of the 75-kDa subunit of mitochondrial complex I by iron. J. Biol. Chem. 276:2001;27685-27692
56. Loeffler D.A., Connor J.R., Juneau P.L., Snyder B.S., Kanaley L., DeMaggio A.J., Nguyen H., Brickman C.M., LeWitt P.A. Transferrin and iron in normal, Alzheimer's disease, and Parkinson's disease brain regions. J. Neurochem. 65:1995;710-724
57. Mann V.M., Cooper J.M., Daniel S.E., Srai K., Jenner P., Marsden C.D., Schapira A.H. Complex I, iron, and ferritin in Parkinson's disease substantia nigra. Ann. Neurol. 36:1994;876-881
58. Manning-Bog A.B., McCormack A.L., Li J., Uversky V.N., Fink A.L., Di Monte D.A. The herbicide paraquat causes up-regulation and aggregation of alpha-synuclein in mice: paraquat and alpha-synuclein. J. Biol. Chem. 277:2002;1641-1644
59. Martins E.A., Robalinho R.L., Meneghini R. Oxidative stress induces activation of a cytosolic protein responsible for control of iron uptake. Arch. Biochem. Biophys. 316:1995;128-134
60. Mochizuki H., Imai H., Endo K., Yokomizo K., Murata Y., Hattori N., Mizuno Y. Iron accumulation in the substantia nigra of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced hemiparkinsonian monkeys. Neurosci. Lett. 168:1994;251-253
61. Nunez M.T., Nunez-Millacura C., Tapia V., Munoz P., Mazariegos D., Arredondo M., Mura C., Maccioni R.B. Iron-activated iron uptake: a positive feedback loop mediated by iron regulatory protein 1. Biometals. 16:2003;83-90
62. Nunez-Millacura C., Tapia V., Munoz P., Maccioni R.B., Nunez M.T. An oxidative stress-mediated positive-feedback iron uptake loop in neuronal cells. J. Neurochem. 82:2002;240-248
63. Olanow C.W. Magnetic resonance imaging in parkinsonism. Neurol. Clin. 10:1992;405-420
64. Ostrerova-Golts N., Petrucelli L., Hardy J., Lee J.M., Farer M., Wolozin B. The A53T alpha-synuclein mutation increases iron-dependent aggregation and toxicity. J. Neurosci. 20:2000;6048-6054
65. Paik S.R., Shin H.J., Lee J.H., Chang C.S., Kim J. Copper(II)-induced self-oligomerization of alpha-synuclein. Biochem. J. 340:1999;821-828
66. Pastore A., Tozzi G., Gaeta L.M., Bertini E., Serafini V., Di Cesare S., Bonetto V., Casoni F., Carrozzo R., Federici G., Piemonte F. Actin glutathionylation increases in fibroblasts of patients with Friedreich's ataxia: a potential role in the pathogenesis of the disease. J. Biol. Chem. 278:2003;42588-42595
67. Pezzella A., d'Ischia M., Napolitano A., Misuraca G., Prota G. Iron-mediated generation of the neurotoxin 6-hydroxydopamine quinone by reaction of fatty acid hydroperoxides with dopamine: a possible contributory mechanism for neuronal degeneration in Parkinson's disease. J. Med. Chem. 40:1997;2211-2216
68. Piemonte F., Pastore A., Tozzi G., Tagliacozzi D., Santorelli F.M., Carrozzo R., Casali C., Damiano M., Federici G., Bertini E. Glutathione in blood of patients with Friedreich's ataxia. Eur. J. Clin. Invest. 31:2001;1007-1011
69. Polymeropoulos M.H., Lavedan C., Leroy E., Ide S.E., Dehejia A., Dutra A., Pike B., Root H., Rubenstein J., Boyer R., Stenroos E.S., Chandrasekharappa S., Athanassiadou A., Papapetropoulos T., Johnson W.G., Lazzarini A.M., Duvoisin R.C., Di Iorio G., Golbe L.I., Nussbaum R.L. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science. 276:1997;2045-2047
70. Przedborski S., Chen Q., Vila M., Giasson B.I., Djaldatti R., Vukosavic S., Souza J.M., Jackson-Lewis V., Lee V.M., Ischiropoulos H. Oxidative post-translational modifications of alpha-synuclein in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. J. Neurochem. 76:2001;637-640
71. Riederer P., Dirr A., Goetz M., Sofic E., Jellinger K., Youdim M.B. Distribution of iron in different brain regions and subcellular compartments in Parkinson's disease. Ann. Neurol. 32(Suppl.):1992;S101-S104
72. Riederer P., Sofic E., Rausch W.D., Schmidt B., Reynolds G.P., Jellinger K., Youdim M.B. Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains. J. Neurochem. 52:1989;515-520
73. Rouault T.A. Post-transcriptional regulation of human iron metabolism by iron regulatory proteins. Blood Cells Mol. Dis. 29:2002;309-314
74. Sengstock G.J., Olanow C.W., Menzies R.A., Dunn A.J., Arendash G.W. Infusion of iron into the rat substantia nigra: nigral pathology and dose-dependent loss of striatal dopaminergic markers. J. Neurosci. Res. 35:1993;67-82
75. Shimura-Miura H., Hattori N., Kang D., Miyako K., Nakabeppu Y., Mizuno Y. Increased 8-oxo-dGTPase in the mitochondria of substantia nigral neurons in Parkinson's disease. Ann. Neurol. 46:1999;920-924
76. Sian J., Dexter D.T., Lees A.J., Daniel S., Agid Y., Javoy-Agid F., Jenner P., Marsden C.D. Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting basal ganglia. Ann. Neurol. 36:1994;348-355
77. Sofic E., Lange K.W., Jellinger K., Riederer P. Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson's disease. Neurosci. Lett. 142:1992;128-130
78. Sofic E., Paulus W., Jellinger K., Riederer P., Youdim M.B. Selective increase of iron in substantia nigra zona compacta of parkinsonian brains. J. Neurochem. 56:1991;978-982
79. Sofic E., Riederer P., Heinsen H., Beckmann H., Reynolds G.P., Hebenstreit G., Youdim M.B. Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain. J. Neural Trans. 74:1988;199-205
80. Sziraki I., Mohanakumar K.P., Rauhala P., Kim H.G., Yeh K.J., Chiueh C.C. Manganese: a transition metal protects nigrostriatal neurons from oxidative stress in the iron-induced animal model of parkinsonism. Neuroscience. 85:1998;1101-1111
81. Takahashi Y., Miyajima H., Shirabe S., Nagataki S., Suenaga A., Gitlin J.D. Characterization of a nonsense mutation in the ceruloplasmin gene resulting in diabetes and neurodegenerative disease. Hum. Mol. Genet. 5:1996;81-84
82. Takanashi M., Mochizuki H., Yokomizo K., Hattori N., Mori H., Yamamura Y., Mizuno Y. Iron accumulation in the substantia nigra of autosomal recessive juvenile parkinsonism (ARJP). Parkinsonism Relat. Disord. 7:2001;311-314
83. Takeuchi Y., Yoshikawa M., Tsujino T., Kohno S., Tsukamoto N., Shiroi A., Kikuchi E., Fukui H., Miyajima H. A case of aceruloplasminaemia: abnormal serum ceruloplasmin protein without ferroxidase activity. J. Neurol. Neurosurg. Psychiatry. 72:2002;543-545
84. Temlett J.A., Landsberg J.P., Watt F., Grime G.W. Increased iron in the substantia nigra compacta of the MPTP-lesioned hemiparkinsonian African green monkey: evidence from proton microprobe elemental microanalysis. J. Neurochem. 62:1994;134-146
85. Theil E.C., Eisenstein R.S. Combinatorial mRNA regulation: iron regulatory proteins and iso-iron-responsive elements (Iso-IREs). J. Biol. Chem. 275:2000;40659-40662
86. Thompson K., Menzies S., Muckenthaler M., Torti F.M., Wood T., Torti S.V., Hentze M.W., Beard J., Connor J. Mouse brains deficient in H-ferritin have normal iron concentration but a protein profile of iron deficiency and increased evidence of oxidative stress. J. Neurosci. Res. 71:2003;46-63
87. Thompson K.J., Shoham S., Connor J.R. Iron and neurodegenerative disorders. Brain Res. Bull. 55:2001;155-164
88. Thong P.S.P. Nuclear microscopic investigations into the elemental changes in the substantia nigra of unilaterally MPTP-lesioned parkinsonian monkeys. Nucl. Instrum. Methods Phys. Res. B. 130:1997;460-467
89. Uversky V.N., Li J., Fink A.L. Metal-triggered structural transformations, aggregation, and fibrillation of human alpha-synuclein. A possible molecular NK between Parkinson's disease and heavy metal exposure. J. Biol. Chem. 276:2001;44284-44296
90. Vile G.F., Tyrrell R.M. Oxidative stress resulting from ultraviolet A irradiation of human skin fibroblasts leads to a heme oxygenase-dependent increase in ferritin. J. Biol. Chem. 268:1993;14678-14681
91. Wesemann W., Blaschke S., Solbach M., Grote C., Clement H.W., Riederer P. Intranigral injected iron progressively reduces striatal dopamine metabolism. J. Neural Trans. Park. Dis. Dement. Sect. 8:1994;209-214
92. Ye F.Q., Allen P.S., Martin W.R. Basal ganglia iron content in Parkinson's disease measured with magnetic resonance. Mov. Disord. 11:1996;243-249
93. Yoritaka A., Hattori N., Uchida K., Tanaka M., Stadtman E.R., Mizuno Y. Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease. Proc. Natl. Acad. Sci. U.S.A. 93:1996;2696-2701
94. Yoshida S., Ektessabi A., Fujisawa S. XANES spectroscopy of a single neuron from a patient with Parkinson's disease. J. Synchrotron. Radiat. 8:2001;998-1000
95. Youdim M.B., Ben-Shachar D., Riederer P. The role of monoamine oxidase, iron-melanin interaction, and intracellular calcium in Parkinson's disease. J. Neural Trans. 32(Suppl.):1990;239-248
96. Youdim M.B., Ben-Shachar D., Riederer P. The possible role of iron in the etiopathology of Parkinson's disease. Mov. Disord. 8:1993;1-12