The relevance of iron in the pathogenesis of Parkinson's disease

Journal of Neurochemistry

Volumn 118, Issue 6, 2011, Pages 939-957

  Sian Hülsmann, Jeswinder ^a   Mandel, Silvia ^b   Youdim, Moussa B H ^b,c   Riederer, Peter ^a  

^a UNIVERSITY OF WÜRZBURG   (Germany)

^b TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

^c Yonsei University   (South Korea)

Author keywords

ferritin; iron; iron related disorders; neurodegenerative diseases; neuromelanin; Parkinsonism subtypes

Indexed keywords

FERRITIN; IRON; NEUROMELANIN; REACTIVE NITROGEN SPECIES; REACTIVE OXYGEN METABOLITE;

AGING; APOPTOSIS; BRAIN LEVEL; CELL DESTRUCTION; DISEASE COURSE; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DOPAMINERGIC NERVE CELL; EXCITOTOXICITY; HUMAN; INFLAMMATION; IRON METABOLISM; LEWY BODY; NERVE CELL DEGENERATION; NIGRONEOSTRIATAL SYSTEM; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN DEGRADATION; REVIEW; SUBSTANTIA NIGRA;

AGING; ANIMALS; FERRITINS; HOMEOSTASIS; HUMANS; IRON; LEWY BODIES; MELANINS; OXIDATIVE STRESS; PARKINSON DISEASE;

EID: 80051801621     PISSN: 00223042     EISSN: 14714159     Source Type: Journal    
DOI: 10.1111/j.1471-4159.2010.07132.x     Document Type: Review

References (173)

1. Aime S., Bergamasco B., Casu M., Digilio G., Fasano M., and, Giraudu S., (2000) Isolation of ÂC NMR characterisation of insoluble proteinaceous fraction from substantia nigra of patients with Parkinson's disease. Mov. Disorders 15, 977-981.
2. Aleyasin H., Rousseaux W. C., Philips M., Kim R. H., Bland J. R., Callaghan S., Slack R. S., During M. J., Mak T. W., and, Park D. S., (2007) The Parkinson's disease gene DJ-1 is also a key regulator of stroke induced damage. Proc. Natl Acad. Sci. USA 107, 18748-18753. (Pubitemid 350210768)
3. Andrew R., Watson D. G., Bet S. A., Midgley J. M., Wenlong H., and, Perry R. K., (1993) The determination of 6-hydroxydopamines and other trace amines in the urine of parkinsonian patients and normal controls. Neurochem. Res. 18, 1175-1177. (Pubitemid 23306353)
4. Barker J. E., Heales S. J., and, Cassidy A., (1996) Depletion of brain glutathione reductase activity: an enzyme susceptible to oxidative stress. Brain Res. 716, 118-122. (Pubitemid 26156603)
5. Bartels A., Willemsen A. T., Kotekaas R., Jong B. M., De Vries R., Klerk O., Portman A., and, Leenders K. L., (2008) Decreased blood brain barrier P-glycoprotein function in the progression of Parkinson's disease, PSP and MSA. J. Neural Transm. 115, 1001-1009.
6. Bartzokis G., Cumming J. L., Markham C. H., Marmarelis P. Z., Treciokas L. J., Tishler T. A., Marder S. R., and, Mintz J., (1999) MRI evaluation of brain iron earlier and later onset Parkinson's disease and normal subjects. Magn. Reson. Imaging 17, 213-222. (Pubitemid 29053180)
7. Bauer M., Karch R., Abrahim A., Wagner C. C., Kletter K., Mueller M., and, Langer O., (2008) Decreased blood-brain barrier P-glycoprotein function with aging. BMC Pharmacol. 8 (Suppl. 1), A48.
8. Beard J. L., and, Connor J. R., (2003) Iron status and neural functioning. Annu. Rev. Nutr. 23, 41-58. (Pubitemid 37059715)
9. Becker G., Seufert J., Reichmann H., and, Reiners K., (1995) Degeneration of substantia nigra in chronic Parkinson's disease visualized by transcranial color-coded real time sonography. Neurology 45, 443-454.
10. Behnke S., Schroeder U., Dillmann U., Bucholz G. G., Schreckenberger M., Fuss G., Reith W., Berg D., and, Krick C. M., (2009) Hyperechogenicity of the substantia nigra in healthy controls is related to MRI changes and to neuronal loss as determined by F-Dopa PET. NeuroImage 47, 1237-1243.
11. Ben-Shachar D., and, Youdim M. B., (1993) Iron, melanin and dopamine interaction: relevance to Parkinson's disease. Prog. Neuropsychopharmacol. Biol. Psychiatry 17, 139-150.
12. Ben-Shachar D., Riederer P., and, Youdim M. B. H., (1991) Iron-melanin interaction and lipid peroxidation: implications for Parkinson's disease. J. Neurochem. 57, 1609-1614. (Pubitemid 21922796)
13. Benzi G., Curti D., and, Pastoris O., (1991) Sequential damage in mitochondrial complexes by peroxidative stress. Neurochem. Res. 16, 1295-1302.
14. Berg D., Becker G., Zeiler B., Tucha O., and, Hofmann E., (1999) Vulnerabilty of the nigrostriatal system as detected by transcranial ultrasound. Neurol 53, 1026-1031. (Pubitemid 29442119)
15. Berg D., Becker G., Riederer P., and, Riess O., (2002a) Iron in neurodegenerative disorders. Neurotoxic Res. 8, 637-653. (Pubitemid 35385963)
16. Berg D., Roggendorf W., Schröder U., et al. (2002b) Echogenicity of the Substantia Nigra: association with increased iron content and marker for susceptibility to nigrostriatal injury. Arch. Neurol. 59, 999-1005. (Pubitemid 34640761)
17. Block M., Zecca L., and, Hong J.-S., (2007) Microglia-mediated neurotoxicity; uncovering the molecular mechanisms. Nat. Rev. Neurosci. 8, 57-69. (Pubitemid 46011999)
18. Boissier de Sauvages F., (1768) Nosologie methodice sistens morbeorum clesses juxte. Sydenhemi mentem and botericorum rodinem. Amsterdam. Fratelli de Tournes.
19. Bolaños J. P., Almeida A., Fernández E., Medina J. M., Land J. M., Clark J. B., and, Heales S. J., (1997) Potential mechanisms for nitric oxide-mediated impairment of brain mitochondrial energy metabolism. Biochem. Soc. Trans. 25, 944-949. (Pubitemid 27416969)
20. Borie C., Gasparini F., Verpillat P., Bonnet A. M., Agid Y., Hetet G., Brice A., Dürr A., and, Grandchamp B., (2002) French Parkinson's disease genetic study group. Association study between iron related genes polymorphism and Parkinson's disease. J. Neurol. 249, 801-804. (Pubitemid 34754212)
21. Braak H., Ghebremedhin E., Rub U., Bratzke H., and, Del Tredici K., (2004) Stages in development of Parkinson's disease related pathology. Cell Tissue Res. 318, 121-134. (Pubitemid 39362633)
22. Byun J., Henderson J. P., Mueller D. M., and, Heinecke J. W., (1999) 8-Nitro-2-deoxyguanosine, a specific marker for reactive oxygen species, is generated by the myeloperoxidase-hydrogen peroxide-nitrite system of activated human phagocytes. Biochemistry 38, 2590-2600.
23. Cass W. A., Grondin R., Anderson A. H., Zhang Z., Hardy P. A., Hussey-Anderson L. K., Rayens W. S., Gerhardt G. A., and, Gash D. M., (2007) Iron accumulation in the striatum predicts ageing-related decline in motor function in rhesus monkeys. Neurobiol. Aging 28, 258-271. (Pubitemid 44894635)
24. Castellani R. J., Siedlak S. L., Perry G., and, Smith M. A., (2000) Sequestration of iron by Lewy bodies in Parkinson's disease. Acta Neuropathol. 100, 111-114. (Pubitemid 30456131)
25. Chen H., Zhang S. M., and, Hernan M. A., (2003) Nonsteroidal anti-inflammmatory drugs and the risk of Parkinson's disease. Arch. Neurol. 60, 1059-1064. (Pubitemid 36975791)
26. Connor J. R., Synder B. S., Beard J. L., Fine R., and, Mufson E., (1992) Regional distribution of iron and iron-regulatory proteins in the brain aging and Alzheimer's disease. J. Neurosci. Res. 31, 327-335.
27. Connor J. R., Boeshore K. L., Bekovic S. A., and, Menzies S. L., (1994) Isoforms of ferritin have a specific cellular distribution in the brain. J. Neurosci. Res. 37, 461-465. (Pubitemid 24105152)
28. Connor J. R., Synder B. S., Arosio P., Loeffler D. A., and, Lewitt P., (1995) A quantitative analysis of isoferritins in selected regions of aged, Parkinsonian and Alzheimer's diseased brains. J. Neurochem. 65, 717-724.
29. Connor J. R., Arosio P., Loeffler D. A., and, Lewitt P., (2004) Decreased transferrin receptor expression by neuromelanin cells in restless leg syndrome. Neurology 62, 1563-1567. (Pubitemid 38608196)
30. Curtis Ar., Fey C., Morris C. M., Bindoff L. A., Ince P. G., Chinery P. F., Coulthard A., Jackson M., et al. (2001) Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease. Nat. Genet. 28, 350-354. (Pubitemid 32702424)
31. Depboylu C., Matusch A., Tribl F., Zory M., Michel P. P., Riederer P., Gerlach M., Becker S., Oertal W. H., and, Hoglinger G. U., (2007) Glia protects neurons against extracellular human neuromelanin. Neurodeg. Dis. 4, 218-226. (Pubitemid 47000414)
32. Dexter D. T., Wells F. R., Agid F., Agid Y., Lees A. J., Jenner P., and, Marsden C. D., (1987) Increased nigral iron content in postmortem parkinsonian brain. Lancet 341, 1219-1220. (Pubitemid 17156630)
33. Dexter D. T., Carter C. J., Wells F. R., Javoy-Agid F., and, Agid Y., (1989a) Basal lipid peroxidation in substantia nigra is increased in Parkinson's disease. J. Neurochem. 52, 381-389. (Pubitemid 19037600)
34. Dexter D. T., Wells F. R., Lees A. J., Agid F., Agid Y., Jenner P., and, Marsden C. D., (1989b) Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson's disease. J. Neurochem. 52, 1830-1836. (Pubitemid 19140770)
35. Dexter D. T., Carter C. J., Wells F. R., Javoy-Agid F., Agid Y., Lees A., Jenner P., and, Marsden C. D., (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, 1953-1975.
36. Dexter D. T., Jenner P., Schapira A. H., and, Marsden C. D., (1992) Alterations in levels of iron, ferritin, and other trace metals in neurodegenerative diseases affecting the basal ganglia.Ann. Neurol 32, S94-S100.
37. Dexter D. T., Sian J., Jenner P., and, Marsden C. D., (1993) Implications of alterations in trace element levels in brain in Parkinson's disease and other neurological disorders affecting the basal ganglia. Adv. Neurol. 60, 273-281.
38. Dexter D. T., Sian J., Rose S., et al. (1994) Indices of oxidative stress and mitochondrial function in individuals with incidental Lewy body disease. Ann. Neurol. 35, 38-44. (Pubitemid 24027604)
39. Double K. L., Maywald M., Schmittel M., Riederer P., and, Gerlach M., (1998) In vitro studies of ferritin iron release and neurotoxicity. J. Neurochem. 70, 2492-2499. (Pubitemid 28252375)
40. Double K. L., Riederer P., and, Gerlach M., (1999) The significance of neuromelanin for neurodegeneration in Parkinson'sdisease. Drug News Perspect. 12, 333-340.
41. Double K. L., Rowe D. B., Carew-Jones F. M., et al. (2009) Anti-melanin antibodies are increased in sera in Parkinson's disease. Exp. Neurol. 217, 297-301.
42. Earle K. M., (1968) Studies on Parkinson's disease including X-ray fluorescent spectroscopy of formalin fixed brain tissue. J. Neuropathol. Exp. Neurol. 27, 1-14.
43. Fahn S., and, Sulzer D., (2004) Neurodegeneration and neuroprotection in Parkinson's disease. NeuroRx 1, 139-154.
44. Fang D., Zhong-ming Q., Zhu L., Wu Xiao M. W., Yung W. H., Ting T. Y., and, Ya K., (2009) l-Dopa neurotoxicity is mediated by up-regulation of DMT1-IRE expression. PLoS ONE 4, e4593.
45. Faucheux B. A., Nillesse N., Damier P., Spik G., Mouatt-Prigent A., et al. (1995) Expression of lactoferritin receptors is increased in the mesencephalon of patients with Parkinson's disease. Proc. Natl Acad. Sci. USA 92, 9603-9607.
46. Faucheux B. A., Damier P., and, Spik G., (2002) Lack of upregulation of ferritin is associated with sustained iron regulatory protein-1 binding activity in the substantia nigra of patients of Parkinson's disease. J. Neurochem. 83, 320-330. (Pubitemid 35191397)
47. Faucheux B. A., Martin M. E., Beaumont C., Hauw J. J., Agid Y., and, Hirsch E. C., (2003) Neuromelanin associated redox active iron is increased in the substantia nigra of patients with Parkinson's disease. J. Neurochem. 86, 1142-1148. (Pubitemid 37022190)
48. Fearnely J. M., and, Lees A. J., (1991) Ageing and Parkinson's disease: substantia nigra regional selectivity. Brain 114, 2283-2301.
49. Fornai F., Schluter O. M., Lenzi P., Gesi M., Ruffoli R., and, Ferruci M., (2005) Parkinson-like syndrome induced by continuous MPTP infusion: convergent roles of the ubiquitin proteasome system and alpha-synuclein. Proc. Natl Acad. Sci. USA 102, 3413-3418. (Pubitemid 40328059)
50. Friedman A., Galazka-Friedman J., and, Koziorowski D., (2009) Iron as a cause of Parkinson disease-a myth or a well established hypothesis? Parkinsonism Relat. Disord. 15 (Suppl. 3), S212-S214.
51. Galazka-Friedman J., Bauminger E. R., and, Friedman A., (1996) Iron in parkinsonian and control substantia nigra: a Moessbauer spectroscopy study. Mov. Disord. 11, 8-16.
52. Gerlach M., Trautwein A., Zecca L., Youdim M. B. H., and, Riederer P., (1995) Moessbauer spectroscopic studies of purified neuromelanin isolated from substantia nigra. J. Neurochem. 65, 923-926.
53. Gerlach M., Double K. L., Youdim M. B. H., and, Riederer P., (2006) Potential sources of increased iron in the substantia nigra of parkinsonian patients. J. Neural Transm. 70, 133-142. (Pubitemid 44622190)
54. Giasson B. I., Duda Jem Murray I. V., Chen Q., and, Souza J. M., (2000) Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. Science 3, 985-989.
55. Gibb W. R., (1992) Melanin, tyrosine hydroxylase, calbindin and substance P in the human mid brain and substantia nigra in relation to nigrostriatal projections and differential neuronal susceptibility in Parkinson's disease. Brain Res. 581, 283-291.
56. Goetz M. E., Double K., Gerlach M., Youdim M. B. H., and, Riederer P., (2004) The relevance of iron in the pathogenesis of Parkinson's disease. Ann. N Y Acad. Sci. 1012, 193-208. (Pubitemid 38455479)
57. Good P. F., Olanow C. W., and, Perl D. P., (1992) Neuromelanin-containing neurons of the substantia nigra accumulate iron and aluminum in Parkinson's disease: a LAMMA study. Brain Res. 593, 343-346.
58. Gorell J. M., Ordidge R. J., Brown G. G., Deniau J. C., Buderer N. M., and, Helpern J. A., (1995) Increased iron-related MRI contrast in the substantia nigra in Parkinson's disease. Neurology 45, 1138-1143.
59. Graham J. M., Paley M. N., Grunewald R. A., Hoggard N., and, Griffiths P. D., (2000) Brain iron deposition in Parkinson's disease imaged using the PRIME magnetic resonance sequence. Brain 123, 2423-2431.
60. Griffiths P. D., Dobson B. R., Jones G. R., and, Clarke D. T., (1999) Iron in the basal ganglia in Parkinson's disease: an in vitro study using X-ray absorption fine structure and cryo-electron microscopy. Brain 122, 667-673. (Pubitemid 29158775)
61. Gutteridge J. M., (1994) Hydroxyl radicals, iron, oxidative stress and neurodegeneration. Ann. N Y Acad. Sci. 738, 201-213.
62. Haacke E. M., Cheng N. Y., House M. J., Liu Q., Neelavalli J., Ogg R. J., Khan A., Ayaz M., Kirsch W., and, Obenaus A., (2005) Imaging iron stores in the brain using magnetic resonance imaging. Magn. Reson. Imaging 23, 1-25. (Pubitemid 40269946)
63. Harley A., Cooper J. M., and, Schapira A. H., (1993) Iron induced oxidative stress and mitochondrial dysfunction: relevance to Parkinson's disease. Brain Res. 627, 349-353. (Pubitemid 23313275)
64. Hashimoto M., Takeda A., Hsu L. J., Takenouchi T., and, Masliah E., (1999) Role of cytochrome c as a stimulator of alpha-synuclein aggregation in Lewy body disease. J. Biol. Chem. 274, 28849-28852.
65. He Y., Thong P. S., Lee T., Leong S. K., Mao B. Y., Dong F., and, Watt F., (2003) Dopaminergic cell death precedes iron elevation in MPTP-injected monkeys. Free Rad. Biol. Med. 35, 540-547. (Pubitemid 37289163)
66. Hirsch E. C., (1994) Biochemistry of Parkinson's disease with special reference to the dopaminergic systems. Mol. Neurobiol. 9, 135-142.
67. Hirsch E. C., and, Faucheux B. A., (1998) Iron metabolism and Parkinson's disease. Mov. Disord. 13, 39-45.
68. Hoeppner J., Prudente-Morrissey L., Herppertz S. C., Benecke R., and, Walter U., (2009) Substantia nigra hyperechogenicity in depressive subjects relates to motor asymmetry and impaired word fluency. Eur. Arch. Psychiatry Clin. Neurosci. 259, 92-97.
69. Hu L., Hittelman W., Lu T., Ji P., Arlinghaus R., et al. (2009) NGAL decreases E-cadherin-mediated cell-cell adhesion and increases cell motility and invasion through Rac1 in colon carcinoma cells. Lab. Invest. 89, 531-548.
70. Hunot S., Boissiere F., and, Faucheux B., (1996) Nitric oxide synthase and neuronal vulnerability in Parkinson's disease. Neuroscience 72, 355-363. (Pubitemid 26111202)
71. Hyun D., Lee M., Halliwell B., and, Jenner P., (2002) Proteasomal dysfunction induced by 4-hydroxy-2,3-transnonenal, an end product of lipid peroxidation: a mechanism contributing to neurodegeneration. J. Neurochem. 83, 360-370. (Pubitemid 35191401)
72. Iacopino A., Christakos S., German D., Sonsalla P. K., and, Altar C. A., (1992) Calindin-D28K containing neurons in animal models of neurodegeneration: possible protection from excitotoxicity. Brain Res. Mol. Brain Res. 13, 251-261.
73. Irvine G. B., El-Agnaf O. M., Shankar G. M., and, Walsh D. M., (2008) Protein aggregation in the brain: the molecular basis for Alzheimer's and Parkinson's disease. Mol. Med. 14, 451-464.
74. Jellinger K., Paulus W., Grundke-Iqbal I., Riederer P., and, Youdim M. B. H., (1990) Brain iron and ferritin in Parkinson's disease and Alzheimer's disease. J. Neural Transm. 2, 327-340.
75. Jellinger K., Kienzl E., Rumpelmair G., Riederer P., Stachelberger H., Ben-Shachar D., and, Youdim M. B., (1992) Iron-melanin complex in substantia nigra of parkinsonian brains: an x-ray microanalysis. J. Neurochem. 59, 1168-1171.
76. Jenner P., (1993) Altered mitochondrial function, iron metabolism and glutathione levels in Parkinson's disease. Acta Neurol. Scand. Suppl. 146, 6-13. (Pubitemid 23251601)
77. Jenner P., and, Olanow C. W., (2006) The pathogenesis of cell death in Parkinson's disease. Neurology 66, S24-S36.
78. Kaur D., Lee D., Ragapolan S., and, Andersen J. K., (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, 593-598.
79. Ke Y., and, Qian Z. M., (2007) Brain iron metabolism: neurobiology and neurochemistry. Prog. Neurobiol. 83, 149-173. (Pubitemid 47484044)
80. Kell D. B., (2009) Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases. BMC Med. Genomics 2, 2.
81. Khedr E., Hamed S. A., Elbeih E., El-Shereef H., Ahamad Y., and, Ahmad S., (2008) Iron states and cognitive abilities in young adults: neuropsychological and neurophysiological assessment. Eur. Arch. Psychiatry Clin. Neurosci. 258, 489-496.
82. Kienzl E., Puchinger L., Jellinger K., Linert W., Stachelberger H., and, Jameson R., (1995) The role of transition metals in the pathogenesis of Parkinson's disease. J. Neurol. Sci. 134, 69-78.
83. Kosta P., Argyrpoulou M. I., and, Markoula S., (2006) MRI evaluation of the basal ganglia size and iron content in patients with Parkinson's disease. J. Neurol. 253, 26-32. (Pubitemid 43157384)
84. Lapenna D., Degioia S., Ciofani G., and, Cuccurullo F., (1995) Captopril induces iron release from ferritin and oxidative stress. J. Pharm. Pharmacol. 47, 59-61.
85. Leveugle B., Faucheux B., Bouras C., Nillesse N., Spik G., Hirsch E., Agid Y., and, Hof P., (1996) Cellular distribution of iron-binding protein lactotransferrin in the mesencephalon of Parkinson's disease. Acta Neuropathol. 91, 566-572. (Pubitemid 26166670)
86. Lewis S., Fotynie T., Blackwell A., Robbins T., Owen A., and, Barker R., (2005) Heterogeneity of Parkinson's disease in the early clinical stages using a data driven approach. J. Neurol. Neurosurg. Psychiatry 76, 343-348. (Pubitemid 40299121)
87. Lhermitte J., Kraus W. M., and, McAlpine A. D., (1924) On the occurrence of abnormal deposits of iron in brain in parkinsonism with special reference to its localisation. J. Neurol. Psychopathology 5, 195-208.
88. Loeffler D. A., Connor J. R., Juneau P. I., Snyder B. S., Kanaley L., DeMaggio A. J., et al. (1995) Transferrin and iron in normal, Alzheimer's disease, and Parkinson's disease brain regions. J. Neurochem. 65, 710-716.
89. Lopiano L., Chiesa M., Digilio G., Giraudo S., Bergamasco B., Torre E., and, Fasano M., (2000) Q-band EPR investigations of neuromelanin control and Parkinson's disease patients. Biochem. Biophys. Acta 1500, 306-312. (Pubitemid 30123061)
90. McGeer P. L., and, McGeer E., (2004) Inflammation and neurodegeneration in Parkinson's disease. Parkinsonism Relat. Disord. 10, S3-S7. (Pubitemid 38510423)
91. McNaught K. S., Belizaire R., Isacson O., Jenner P., and, Olanow C. W., (2003) Altered proteasomal function in sporadic Parkinson's disease. Exp. Neurol. 179, 38-46. (Pubitemid 36062617)
92. Miwa C. P., de Lima M. N., Scalco F., Vedana G., Mattos R., Fernandez L. L., Hilbig A., Schröder K., and, Vianna M. R., (2010). Neonatal iron treatment increases apoptotic markers in hippocampal and cortical areas of adult rats. Neurotoxicity Res. [Epub ahead of print] PMID: 20369315.
93. Mizuno Y., Ohta S., Tanaka M., Takamiya S., Suzuki K., et al. (1989) Deficiencies in complex I subunits of the respiratory chain in Parkinson's disease. Biochem. Biophys. Res. Commun. 163, 1450-1455. (Pubitemid 19244751)
94. Montine K. S., Quinn J. F., Zhang J., Fessel J. P., and, Roberts L. J., 2nd, Morrow J. D., and, Montine T. J., (2004) Isoprostanes and related products of lipid peroxidation in neurodegenerative diseases. Chem. Phys. Lipids 128, 117-124. (Pubitemid 38167381)
95. Moos T., and, Morgan E. H., (2004) The metabolism of neuronal iron and its pathogenic role in neurological disease. Ann. N Y Acad. Sci. 1012, 14-26. (Pubitemid 38453512)
96. Moran L. B., and, Graeber M. B., (2008) Towards a pathway definition of Parkinson's disease: a complex disorder with links to cancer, diabetes and inflammation. Neurogenetics 9, 1-13.
97. Morawski M., Meinecke Ch., Reinert T., Dorffel A. C., Riederer P., Arendt T., and, Butz T., (2005) Determination of trace elements in the human substantia nigra. Nucl. Instrum. Methods Phys. Res. B 231, 224-228.
98. Morris C. M., and, Edwardson J. A., (1994) Iron histochemistry of the substantia nigra in Parkinson's disease. Neurodegeneration 3, 277-282.
99. Muench G., Lüth H. J., Wong A., Arendt T., Hirsch E., et al. (2000) Crosslinking of alpha-synuclein by advanced glycation end products-an early pathophysiological step in Lewy body formation? J. Chem. Neuroanat. 20, 253-257. (Pubitemid 32162884)
100. Naoi M., Maruyama W., Yi H., Yamaaoka Y., Shagamoto-Nagai M., Akao Y., Gerlach M., and, Tanaka Riederer P., (2008) Neuromelanin selectively induces apoptosis in dopaminergic SH-SY5Y cells by deglutathionylation in mitochondria: involvement of protein and melanin component. J. Neurochem. 105, 2489-2500. (Pubitemid 351782270)
101. Napolitano A., Crescenzi O., Pezzella A., and, Prota G., (1995) Generation of neurotoxin 6-hydroxydopamine by peroxidase/hydrogen peroxide oxidation of dopamine. J. Med. Chem. 38, 917-922.
102. Nemeth E., (2008) Iron regulation and erythropoesis. Curr. Opin. Hematol. 15, 169-175.
103. Oesterreicher E., Sengstock G. J., Riederer P., Olanow C. W., Dunn A. J., and, Arendash G., (1994) Degeneration of nigrostriatal dopaminergic neurons increases iron within the substantia nigra: a histochemical and neurochemical study. Brain Res. 660, 8-18. (Pubitemid 24301248)
104. Olivares D., Huang X., Branden L., Greig N. H., and, Rogers J. T., (2009) Physiological and pathological role of alpha synuclein in Parkinson's disease through iron mediated oxidative stress. The role of putative iron responsive element. Int. J. Mol. Sci. 10, 1226-1260.
105. Orr C. F., Rowe D. B., and, Halliday G. M., (2002) An inflammatory review of Parkinson's disease. Prog. Neurobiol. 68, 325-340. (Pubitemid 36071510)
106. Orr C. F., Rowe D. B., Mizuno Y., Mori H., and, Halliday G., (2005) A possible role for humoral immunity in the pathogenesis of Parkinson's disease. Brain 128, 2665-2674. (Pubitemid 41552950)
107. Ostrerova-Golts N., (2000) The A53T alpha-synuclein mutation increases iron dependent aggregation and toxicity. J. Neurochem. 20, 6048-6054. (Pubitemid 30658398)
108. Parkinson J., (1817). An essay on the shaking palsy. J. Neuropsychiatry Clin. Neurosci. 2002 Spring; 14: 223-236; discussion 222.
109. Perez R. G., and, Hastings T. G., (2004) Could a loss of alpha-synuclein function put dopaminergic neurons at risk? J. Neurochem. 89, 1318-1324. (Pubitemid 38802653)
110. Polymeropoulos M. H., Lavedan C., Leroy E., Ide S. E., Dehejia A., Dutra A., et al. (1997) Mutation in the alpha synuclein gene identified in families with Parkinson's disease. Science 276, 2045-2047. (Pubitemid 27443610)
111. Ponka P., (2004) Hereditary causes of distribution iron homeostasis in the central nervous system. Ann. N Y Acad. Sci. 1012, 267-281. (Pubitemid 38453531)
112. Przedborksi S., and, Vila M., (2001) MPTP: a review of its mechanisms of neurotoxicity. Clin. Neurosci. Res. 1, 407-418. (Pubitemid 33665559)
113. Qian Z. M., and, Wang Q., (1998) Expression of iron transport proteins and excessive iron accumulation in the brain in neurodegenerative disorders. Brain Res. Brain Res. Rev. 27, 257-267. (Pubitemid 28389311)
114. Rausch W. D., Hirata Y., Nagatsu T., Riederer P., and, Jellinger K., (1988) Tyrosine hydroxylase activity in caudate nucleus from Parkinson's disease: effects of iron and phosphorylating agents. J. Neurochem. 50, 202-208. (Pubitemid 18023500)
115. Reichmann H., and, Riederer P., (1989) Biochemische Analyse der Atmungskettenkomplexe verschiedener Hirnregionen von Patienten mit M. Parkinson und anderen Basalganglienerkrankungen. Symposium zu einem Foerderschwerpunkt des BMFT 44, 23-25.
116. Reinheckel T., Sitte N., and, Ulrich O., (1998) Comparitive resistance of the 20S and 26S proteosames to oxidative stress. Biochem. J. Biol. Chem. 274, 23787-23793.
117. Riederer P., and, Wesemann W., eds (1995) Parkinson's disease: experimental models and therapy. J. Neural Transm. Suppl. 46. Springer Verlag Wien/New York, Wien.
118. Riederer P., Sofic E., Rausch W. D., Kruzik P., and, Youdim M. B. H., (1985) Dopaminforschung heute und morgen -l-dopa in der Zukunft, in l-Dopa Substitution der Parkinson-Krankheit (, Riederer P., and, Umek H., eds), pp. 127-144. Springer Verlag Wien, New York.
119. Riederer P., Rausch W. D., Schmidt B., Kruzik P., and, Konradi C., (1988) Biochemical fundamentals of Parkinsons's disease. Mt Sinai J. Med. 55, 21-28.
120. Riederer P., Sofic E., Rausch W. D., Schmidt B., Reynolds G. P., Jellinger K., and, Youdim M. B. H., (1989) Transition metals, ferritin, glutathione and ascorbic acid in parkinsonian brains. J. Neurochem. 52, 515-520. (Pubitemid 19037617)
121. Reif D., and, Simmons R., (1990) Nitric oxide mediates iron release from ferritin. Arch. Biochem. Biophys. 283, 537-541.
122. Romanos M., Weise D., Schliesser M., Schecklmann M., Löffler J., Warnke A., Gerlach M., Classen J., and, Mehler-Wex C., (2010) Structural abnormality of the substantia nigra in children with attention-deficit hyperactivity disorder. J. Psychiatry Neurosci. 35, 55-58.
123. Ryvlin P., Broussolle E., Piollet H., Viallet F., Khalfallah Y., and, Chazot G., (1995) Magnetic resonance imaging evidence of decreased putamenal iron content in idiopathic Parkinson's disease. Arch. Neurol. 52, 583-588.
124. Salazar J., Mena N., Hunot S., Prigent A., Alvarez-Fischer D., et al. (2008) Divalent metal transporter (DMTI) contributes to the neurodegeneration in animal models of Parkinson's disease. Proc. Natl Acad. Sci. USA 105, 18578-18583.
125. Saper C. B., (1999) 'Life a thief in the night": the selectivity of degeneration in Parkinson's disease. Brain 122, 1401-1402. (Pubitemid 29374119)
126. Schapira A. H., Cooper J. M., Dexter D. T., Jenner P., Clark J. B., and, Marsden C. D., (1989) Mitochondrial complex 1 deficiency in Parkinson's disease. Lancet 1, 1269. (Pubitemid 19140359)
127. Schipper H. M., (2000) Heme oxygenase-1, role in brain ageing and neurodegeneration. Exp. Gerontol. 35, 821-830.
128. Schipper H. M., (2004) Heme oxygenase expression in human central nervous system disorders. Free Radic. Biol. Med. 37, 1995-2011. (Pubitemid 39491319)
129. Schmidt M. B., (1940) Störungen des Eisenstoffwechsels und ihre Folgen. Ergebnisse der Pathologie XXXV, 105-208.
130. Seutin V., Shen K. Z., North R. A., and, Johnson S. W., (1996) Sulfonylurea-sensitive potassium current evoked by sodium-loading in rat midbrain dopamine neurons. Neuroscience 71, 709-719. (Pubitemid 26069929)
131. Shamoto-Nagai M., Maruyama W., Akao Y., Osawa T., Tribl F., Gerlach M., Zecca L., Riederer P., and, Naoi M., (2004) Neuromelanin inhibits enzymatic activity of 26S proteosome in human dopaminergic SH-SY5Y cells. J. Neural Transm. 111, 1253-1265. (Pubitemid 39468389)
132. Shamoto-Nagai M., Maruyama W., Hashizume Y., Yoshida M., Osawa T., Riederer P., and, Naoi M., (2007) In parkinsonian substantia nigra, alpha-synuclein is modified by acrolein, a lipid peroxidation product and accumulates in the dopamine neurons with inhibition of proteasome activity. J. Neural Transm. 114, 1559-1567. (Pubitemid 350212012)
133. Shults C. W., (2006) Lewy bodies. Proc Natl. Acad Sci USA 103, 1661-1668. (Pubitemid 43228751)
134. Sian J., Dexter D. T., and, Jenner P., (1991) Decrease in nigral glutathione in Parkinson's disease. Br. J. Pharmacol. 104, 281.
135. Sian J., Dexter D. T., Lees A. J., Daniel S., Jenner P., and, Marsden C. D., (1994a) Glutathione-related enzymes in brain in Parkinson's disease. Ann. Neurol. 36, 356-361. (Pubitemid 24280056)
136. Sian J., Dexter D. T., Jenner P., Lees A. J., Daniel S., Agid Y., Javoy-Agid F., Jenner P., and, Marsden C. D., (1994b) Alterations in glutathione levels in neurodegenerative disorders affecting the basal ganglia. Ann. Neurol. 36, 348-355. (Pubitemid 24280055)
137. Sofic E., Riederer P., Heinsen G., and, Youdim M. B. H., (1988) Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain J. Neural Transm. 74, 199-205.
138. Sofic E., Lange K. W., Jellinger K., and, Riederer P., (1992) Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson's disease. Neurosci. Lett. 142, 128-130.
139. Sofic E., Sapcanin A., Tahirovic I., Gavrankapetanovic I., Jellinger K., Reynolds G. P., Tatschner T., and, Riederer P., (2006) Antioxidant capacity in postmortem brain tissues of Parkinson's and Alzheimer's diseases. J. Neural Transm. Suppl. 71, 39-43. (Pubitemid 351412105)
140. Spillantini M. G., and, Goedert M., (2000) The alpha-synucleinopathies: Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Ann. N Y Acad. Sci. 920, 16-27. (Pubitemid 32056547)
141. Stankiewicz J., Scott S. P., Neema M., Arora A., Batt C., and, Bakshi R., (2007) Iron in chronic brain disorders: imaging and neurotherapeutic implications. Neurotherapeutics 4, 371-386. (Pubitemid 46962416)
142. Sulzer D., and, Zecca L., (2000) Untraneuronal dopamine-quinone synthesis: a review. Neurotox. Res., 1, 181-195.
143. Sulzer D., Bogulavsky J., Larsen K., Behr G., et al. (2000) Neuromelanin biosynthesis driven by excess cytosolic catecholamines not accumulated by synaptic vesicles. Proc. Natl Acad. Sci. USA, 87, 11869-11874.
144. Tan K. H., Purcell W. M., Heales S. J., McLeod J. D., and, Hurst R. D., (2002) Evaluation of the role of P-glycoprotein in inflammation induced blood-brain barrier damage. Neuroreport 13, 2593-2597. (Pubitemid 36143569)
145. Tanner C. M., Ottman R., Goldman S. M., Ellenberg J., Chan P., Mayeux R., et al. (1999) Parkinson's disease in twins: an etiologic study. JAMA 281, 341-366.
146. Tribl F., Gerlach M., Marcus K., Asan E., Tatschner A., Meyer H. E., Bringmann G., and, Riederer P., (2005) Subcellular proteomics of neuromelanin granules isolated from the human brain. Mol. Cell Proteomics 4, 945-957. (Pubitemid 41309152)
147. Tribl F., Asan E., Arzberger T., Tatschner T., Lagenfeld E., Meyer H. E., Bringmann G., Riederer P., et al. (2009) Identification of l-ferritin in neuromelanin granules of the substantia nigra-a targeted proteomics approach. Mol. Cell Proteomics 8, 1832-1838.
148. Uitti R. J., Rajput A. H., Rozdilsky B., Bickis M., Wollin T., and, Yuen W. K., (1989) Regional metal concentrations in Parkinson's disease, other chronic neurological disease, and control brains. Can. J. Neurol. Sci. 16, 310-314. (Pubitemid 19213592)
149. Volles M. J., Lees S. J., Rochert J. C., Shtilerman M. D., Ding T. T., Kessler J. C., et al. (2001) Vesicle permeabilisation by protofibrillar alpha-synuclein: implications for the pathogenesis and treatment of Parkinson's disease. Biochemistry 40, 7812-7819. (Pubitemid 32622972)
150. Vymazal J., Righini A., Brooks R. A., Canesi M., Mariani C., Leonardi M., and, 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, 489-495. (Pubitemid 29206821)
151. Wallis L. I., Paley M. N., Graham J. M., Grunewald R. A., Wignall E. L., Joy H. M., and, Griffiths P. D., (2008) MRI assessment of basal ganglia iron deposition in Parkinson's disease. J. Magn. Reson. Imaging 28, 1061-1067.
152. Walter U., Hoeppner J., Prudente-Morrissey L., Horowski S., Herpertz S. C., and, Benecke R., (2007) Parkinson's disease-like midbrain sonography abnormalities are frequent in depressive disorders. Brain 130 (Pt 7), 1799-1807. (Pubitemid 47343787)
153. Ward W. C., Zucca F. A., Bellei C., Zecca L., and, Simon J. D., (2009) Neuromelanins in various regions of human brain are associated with native and oxidized isoprenoid lipids. Arch. Biochem. Biophys. 484, 94-99.
154. Weinreb O., Amit T., Bar-Am O., and, Youdim M. B., (2010) Rasagiline: a novel anti-parkinsonian monoamine oxidase-b inhibitor with neuroprotective activity. Prog. Neurobiol. 92, 330-344.
155. Weizer-Stern O., Adamsky K., Amariglio N., Levin C., et al. (2006) Downregulation of hepcidin and haemojuvelin expression in the hepatocyte cell-line HepG2 induced by thalassaemic sera. Br. J. Haematol. 135, 129-138. (Pubitemid 44337673)
156. Wesemann W., Solbach M., Nafe R., Grote C., Sontag K. H., Riederer P., Jellinger K., Mennel H. D., and, Clement H. W., (1995) Effect of lazaroid U-74389 on iron-induced reduction of striatal dopamine metabolism. J. Neural Transm. 46, 175-182. (Pubitemid 26046558)
157. Wills A. J., Sawle G. V., Guilbert P. R., and, Curtis A. R., (2002) Palatal tremor and cognitive decline in neuroferritinopathy. J. Neurol. Neurosurg. Psychiatry, 73, 91-93.
158. Wilms H., Rosenstiel P., Sievers J., Deuschi G., Zecca L., and, Lucius R., (2003) Activation of microglia by human neuromelanin is NF-kappaB dependent and involves p38 mitogen-activated protein kinase; implications for Parkinson's disease. FASEB J. 17, 500-502.
159. Wichmann T., and, DeLong M. R., (1993) Pathophysiology of parkinsonian motor abnormalities. Adv. Neurol. 60, 53-61.
160. Wu L. J., Leenders A. G., Cooperman S., Meyron-Holtz E., Smith S., Land W., et al. (2004) Expression of iron transporter ferroportin in synaptic vesicles and the blood brain barrier. Brain Res. 1001, 108-117. (Pubitemid 38221533)
161. Yoritaka A., Hattori N., and, Uchida K., (1996) Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson's disease. Proc. Natl Acad. Sci. USA 93, 2696-2701. (Pubitemid 26114311)
162. Yoshida T., Tanaka M., Sotomatsu A., and, Hirai S., (1995) Activated microglia cause superoxide-mediated release of iron from ferritin. Neurosci. Lett. 190, 21-24.
163. Youdim M. B. H., (2003) Rasagiline: an anti-Parkinson drug with neuroprotectivity. Exp. Rev. Neurother. 3, 737-749.
164. Youdim M. B. H., and, Riederer P., (1993) The role of iron in senescence of dopaminergic neurons in Parkinson's disease. J. Neural Transm. Suppl. 40, 57-67. (Pubitemid 24005557)
165. Youdim M. B. H., and, Riederer P., (2004) Iron in the brain, normal and pathological, in Encyclopedia of Neuroscience (, Adelman G., and, Smith B., eds), pp. 984-987. Elsevier, Amsterdam.
166. Yu H. C., Feng S. F., Chao P. L., and, Lin A. M., (2010). Anti-inflammatory effect of pioglitazone on iron-induced oxidative injury in the nigrostriatal dopaminergic system. Neuropathol. Appl. Neurobiol. 36, 612-622.
167. Zecca L., Gallorini M., Schunermann V., Trautwein A. X., and, Gerlach M., (2001) Iron, neuromelanin and ferritin of normal subjects at different ages, consequences for iron storage and neurodegenerative processes. J. Neurochem. 76, 1766-1773. (Pubitemid 32221116)
168. Zecca L., Tampellini D., Gatti A., Crippa R., Eisner M., Sulzer D., et al. (2002) The neuromelanin of human substantia nigra and its interaction with metals. J. Neural Transm. 109, 663-672. (Pubitemid 34810764)
169. Zecca L., Youdim M. B. H., Riederer P., Connor J. R., and, Crichton R. R., (2004) Iron, brain ageing and neurodegenerative disorders. Nat. Rev. Neurosci. 5, 863-873. (Pubitemid 39482155)
170. Zecca L., Berg D., Arzberger T., Ruprecht P., Rausch W. D., Musicco M., Tampellini D., Riederer P., Gerlach M., and, 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, 1278-1285. (Pubitemid 41645902)
171. Zhu M., Rajamani S., Kaylor J., Hans Zhou F., et al. (2004) The flavonoids baicalein inhibits fibrilliation of alpha synuclein and disaggregates existing fibrils. J. Biol. Chem. 279, 26846-26857. (Pubitemid 38812518)
172. Zimprich A., Biksup S., Leitner P., et al,. (2004) Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44, 601-607. (Pubitemid 39531225)
173. Zucca F. A., Bellei C., Giannelli S., Terreni M. R., Gallorini M., Rizzio E., Pezzoli G., Albertini A., and, Zecca L., (2006) Neuromelanin and iron in human locus coeruleus and substantia nigra during aging: consequences for neuronal vulnerability. J. Neural Transm. 113, 757-767. (Pubitemid 43847169)