Mitochondrial dysfunction and oxidative stress in Parkinson's disease

Neurochemical Research

Volumn 33, Issue 3, 2008, Pages 589-597

  Onyango, Isaac G ^a,b  

^a UNIVERSITY OF VIRGINIA   (United States)

^b UNIVERSITY OF VIRGINIA   (United States)

Author keywords

Cybrids; Environmental toxins; Lewy bodies; Mitochondrial dysfunction; MPTP; mtDNA; Neurodegeneration; Oxidative stress; Parkinson's disease; Proteasome; Rotenone

Indexed keywords

CELECOXIB; CYCLOOXYGENASE 2 INHIBITOR; MITOCHONDRIAL DNA; NONSTEROID ANTIINFLAMMATORY AGENT; PIOGLITAZONE; PROTEASOME;

CELL LOSS; DISORDERS OF MITOCHONDRIAL FUNCTIONS; HEREDITY; HUMAN; INFLAMMATION; MITOCHONDRION; MUTATION; NERVE CELL; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PRIORITY JOURNAL; REVIEW;

ANIMALS; DISEASE MODELS, ANIMAL; DNA, MITOCHONDRIAL; HUMANS; INFLAMMATION; MITOCHONDRIAL DISEASES; OXIDATIVE STRESS; PARKINSON DISEASE; PROTEASOME ENDOPEPTIDASE COMPLEX; SIGNAL TRANSDUCTION;

ANIMALIA;

EID: 38949146348     PISSN: 03643190     EISSN: None     Source Type: Journal    
DOI: 10.1007/s11064-007-9482-y     Document Type: Review

References (135)

1. Abou-Sleiman P, Muqit M, Wood N (2006) Expanding insights of mitochondrial dysfunction in Parkinson's disease. Nat Rev Neurosci 7:207-219
2. Alam Z, Daniel S, Lees A, Marsden D, Jenner P, Halliwell B (1997) A generalised increase in protein carbonyls in the brain in Parkinson's but not incidental Lewy body disease. J Neurochem 69:1326-1329
3. Allan S, Rothwell N (2001) Cytokines and acute neurodegeneration. Nat Rev Neurosci 2:734-744
4. Arimoto T, Bing G (2003) Up-regulation of inducible nitric oxide synthase in the substantia nigra by lipopolysaccharide causes microglial activation and neurodegeneration. Neurobiol Dis 12:35-45
5. Arimoto T, Choi D, Lu X, Liu M, Nguyen X, Zheng N, Stewart C, Kim H, Bing G (2006) Interleukin-10 protects against inflammation-mediated degeneration of dopaminergic neurons in substantia nigra. Neurobiol Aging 28:894-906
6. Banati R, Gehrmann J, Schubert P, Kreutzberg GW (1993) Cytotoxicity of microglia. Glia 7:111-118
7. Beal M (2003) Bioenergetic approaches for neuroprotection in Parkinson's disease. Ann Neurol 53:S39-S47
8. Beal M (2005) Mitochondria take center stage in aging and neurodegeneration. Ann Neurol 58:495-505
9. Bender A, Krishnan K, Morris C, Taylor G, Reeve A, Perry R, Jaros E, Hersheson J, Betts J, Klopstock T, Taylor R, Turnbull D (2006) High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet 38:515-517
10. Berger J, Glitza I (2003) Von's Economo's Encephalitis. In: Nath A Jr. (ed) Clinical neurovirology. Marcel Dekker, New York, p 523-542
11. Betarbet R, Sherer T, MacKenzie G, Garcia-Osuna M, Panov A, Greenamyre J (2000) Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nature Neurosci 3:1301-1306
12. Biglan K, Ravina B (2007) Neuroprotection in Parkinson's disease: an elusive goal. Semin Neurol 27:106-112
13. Blum D, Wu Y, Nissou M, Arnaud S, Benabid AL, Verna JM (1997) P53 and bax activation in 6-hydroxydopamine-induced apoptosis in PC12 cells. Brain Res 751:139-142
14. Bossy Wetzel E, Schwarzenbacher R, Lipton S (2004) Molecular pathways to neurodegeneration. Nat Med 10:S2-S9
15. Casali C, Bonifati V, Santorelli F, Casari G, Fortini D, Patrignani A, Fabbrini G, Carrozzo R, D'Amati G, Locuratolo N, Vanacore N, Damiano M, Pierallini A, Pierelli F, Amabile G, Meco G (2001) Mitochondrial myopathy, parkinsonism, and multiple mtDNA deletions in a Sephardic Jewish family. Neurology 56:802-805
16. Casals J, Elizan T, Yahr M (1998) Postencephalitic parkinsonism-a review. J Neural Transm 105:645-676
17. Casetta I, Govoni V, Granieri E (2005) Oxidative stress, antioxidants and neurodegenerative diseases. Curr Pharm Des 11:2033-2052
18. Cassarino DS, Halvorsen EM, Swerdlow RH, Abramova NN, Parker WD Jr, Sturgill TW, Bennett JP Jr (2000) Interaction among mitochondria, mitogen-activated protein kinases, and nuclear factor-kappaB in cellular models of Parkinson's disease. J Neurochem 74(4):1384-1392
19. Castano A, Herrera A, Cano J, Machado A (1998) Lipopolysaccharide intranigral injection induces inflammatory reaction and damage in nigrostriatal dopaminergic system. J Neurochem 70:1584-1592
20. Chalmers R, Brockington M, Howard R, Lecky B, Morgan-Hughes J, Harding A (1996) Mitochondrial encephalopathy with multiple mitochondrial DNA deletions: a report of two families and two sporadic cases with unusual clinical and neuropathological features. J Neurol Sci 143:41-45
21. Chen H, Zhang S, Hernan M, Schwartzschild M, Willett W, Colditz G, Speizer F, Ascherio A (2003) Nonsteriodal anti-inflammatory drugs and the risk of Parkinson's disease. Arch Neurol 60:1059-1064
22. Chen L, Thiruchelvam M, Madura K, Richfield E (2006) Proteasome dysfunction in aged human alpha-synuclein transgenic mice. Neurobiol Dis 23:120-126
23. Chiueh C, Haung S, Murphy D (1992) Enhanced hydroxyl radical generation by 2′-methyl analog of MPTP: suppression by clorgyline and deprenyl. Synapse 11:346-348
24. Chu C, Levinthal D, Kulich S, Chalovich E, DeFranco D (2004) Oxidative neuronal injury: the dark side of ERK1/2. Eur J Biochem 271:2060-2066
25. Chu C, Zhu J-H (2003) Subcellular compartmentalization of P-ERKs in the Lewy body disease substantia nigra. Ann NY Acad Sci 991:288-290
26. Ciccetti F, Brownell A, Williams K, Chen Y, Livni E, Isacson O (2002) Neuroinflammation of the nigrostriatal pathway during progressive 6-OHDA dopamine degeneration in rats monitored by immunohistochemistry and PET imaging. Eur J Neurosci 15:991-998
27. Clark I, Dodson M, Jiang C, Cao J, Huh J, Seol J, Yoo S, Hay Ba, Guo M (2006) Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 441:1162-1166
28. Coelln R, Kugler S, Bahr M, Weller M, Dichgans J, Schulz J (2001) Rescue from death but not from functional impairment: caspase inhibition protects dopaminergic cells against 6-hydroxydopamine induced apoptosis but not against the loss of their terminals. J Neurochem 77:263-273
29. Cooper J, Daniel S, Marsden C, Schapira A (1995) L-dihydroxyphenylalanine and complex I deficiency in Parkinson's disease brain. Mov Disord 10:295-297
30. Crouser E, Julian M, Blaho D, Pfeiffer D (2002) Endotoxin-induced mitochondrial damage correlates with impaired respiratory activity. Crit Care Med 30:276-284
31. Czlonkowska A, Kohuknika M, Kurkowska-Jatrzebska I, Czlonkowski A (1996) Microglial reaction in MPTP (1-methyl-4phenyl-1,2,3,6-tetrahydropyridine) induced Parkinson's disease mice model. Neurodegeneration 5:137-143
32. Darios F, Corti O, Lucking C, Hampe C, Muriel M, Abbas N, Gu W, Hirsch E, Rooney T, Ruberg M, Brice A (2003) Parkin prevents mitochondrial swelling and cytochrome c release in mitochondria-dependent cell death. Hum Mol Genet 12:517-526
33. Dauer W, Przedborski S (2003) Parkinson's disease: mechanisms and models. Neuron 39:889-909
34. De Coo I, Renier W, Ruitenbeek W, Ter Laak H, Bakker M, Schagger H, Van Oost B, Smeets H (1999) A 4-base pair deletion in the mitochondrial cytochrome b gene associated with Parkinsonism/MELAS overlap syndrome. Ann Neurol 45:130-133
35. de Lau L, Breteler M (2006) Epidemiology of Parkinson's disease. Lancet Neurol 5:525-535
36. Dexter D, Wells F, Agid F, Agid Y, Lees AJ, Jenner P, Marsden CD (1987) Increased nigral iron content in postmortem parkinsonian brain. Lancet 8569:1219-1220
37. Ekstrand M, Terzioglu M, Galter D, Zhu S, Hofstetter C, Lindqvist E, Thams S, Bergstrand A, Hansson F, Trifunovic A, Hoffer B, Cullheim S, Mohammed A, Olson L, Larsson N (2007) Progressive parkinsonism in mice with respiratory-chain-deficient dopamine neurons. Proc Natl Acad Sci USA 104:1325-1330
38. Elkon H, Melamed E, Offen D (2004) Oxidative stress, induced by 6-hydroxydopamine, reduces proteasome activities in PC12 cells: implications for the pathogenesis of Parkinson's disease. J Mol Neurosci 24:387-400
39. Fall CP, Bennett JP Jr (1999) Visualization of cyclosporin A and Ca2+-sensitive cyclical mitochondrial depolarizations in cell culture. Biochim Biophys Acta 1410(1):77-84
40. Feng Z, Wang T, Li D, Fung P, Wilson B, Liu B, Ali S, Langenbach R, Hong J (2002) Cyclooxygenase-2-deficient mice are resistant to 1-methyl-4-phenyl-1,2, 3,6-tetradydropyridine-induced damage of dopaminergic neurons in the substantia nigra. Neurosci Lett 329:354-358
41. Fisher J, Mizrahi T, Schori H, Yoles E, Levkovitch-Verbin H, Haggaig S, Revel M, Schwartz M (2001) Increased post-traumatic survival of neurons in IL-6-knockout mice on a background of EAE susceptibility. J Neuroimmunol 119:1-9
42. Friedlander R (2003) Apoptosis and caspases in neurodegenerative diseases. N Engl J Med 348:1365-1375
43. Gao H, Hong J, Zhang W, Liu B (2002) Distinct role for microglia in rotenone-induced degeneration of dopaminergic neurons. J Neurosci 22:782-790
44. Gao H, Liu B, Zhang W, Hong J (2003) Synergistic dopaminergic neurotoxicity of MPTP and inflammogen lipopolysaccharide: relevance to the etioloy of Parkinson's disease. FASEB J 17:1957-1971
45. Gayle D, Ling Z, Tong C, Landers T, Lipton J, Carvey P (2002) Lipopolysacchride (LPS)-induced dopamine cell loss in culture: roles of tumor necrosis factor-alpha, interleukin-1beta, and nitric oxide. Brain Res Dev 133:27-35
46. Ghee M, Fournier A, Mallet J (2000) Rat alpha-synuclein interacts with Tat binding protein 1, a component of the 26S proteasomal complex. J Neurochem 75:2221-2224
47. Gomez-Santos C, Ferrer I, Reiriz J, Vinals F, Barrachina M, Ambrosio S (2002) MPP+ increases α-synuclein expression and ERK/MAP-kinase phosphorylation in human neuroblastoma SH-SY5Y cells. Brain Res 935:32-39
48. Gu M, Cooper J, Taanman J, Schapira A (1998) Mitochondrial DNA transmission of the mitochondrial defect in Parkinson's disease. Ann Neurol 44:177-186
49. Gu Z, Nakamura T, Yao D, Shi Z, Lipton S (2005) S-nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration. Cell Death Differ 12:1202-1204
50. Hald A, Lotharius J (2005) Oxidative stress and inflammation in Parkinson's disease: is there a casual link? Exp Neurol 193:279-190
51. Halliwell B, Gutteridge J (1999) Oxidative stress in PD. In: Halliwell B, Gutteridge J (eds) Free radicals in biology and medicine. Oxford University Press, New York pp 744-758
52. Hartley A, Stone J, Heron C, Cooper J, Schapira A (1994) Complex I inhibitors induce dose-dependent apoptosis in PC12 cells: relevance to Parkinson's disease. J Neurochem 63:1987-1990
53. Hartmann A, Hunot S, Michel PP, Muriel MP, Vyas S, Faucheux BA, Mouatt-Prigent A, Turmel H, Srinivasan A, Ruberg M, Evan GI, Agid Y, Hirsch EC (2000) Caspase-3: a vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease. Proc Natl Acad Sci USA 97(6):2875-2880
54. Hattori N, Tanaka M, Ozawa T, Mizuno Y (1991) Immunohistochemical studies on complexes I, II, III, IV of mitochondria in Parkinson's disease. Ann Neurol 30:563-571
55. He Y, Appel S, Le W (2001) Minocycline inhibits microglial activation and protects nigral cells after 6-hydroxydopamine injection into mouse striatum. Brain Res 909:187-193
56. Hemmer K, Fransen I, Vanderstichele H, VanmeChelen E, Heuschling P (2001) An in vitro model for the study of microglial-induced neurodegeneration: involvement of nitric oxide and tumour necrosis factor-alpha. Neurochem Int 38:557-565
57. Hererra A, Castano A, Venero J, Cano J, Machado A (2000) The single intranigral injection of LPS as a new model for studying the selective effects of inflammatory reactions on dopaminergic system. Neuorobiol Dis 7:429-447
58. Hirsh E, Hunot S, Damier P, Faucheux B (1998) Glial cells and inflammation in Parkinson's disease: a role in neurodegeneration?. Ann Neurol 44:S115-S120
59. Hunter R, Dragicevic N, Seifert K, Choi D, Liu M, Kim H, Cass W, Sullivan P, Bing G (2007) Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system. J Neurochem 100:1375-1386
60. Iravani M, Kashell K, Rose S, Jenner P (2002) Involvement of inducible nitric oxide synthase in inflammation-induced dopaminergic neurodegeneration. Neuroscience 110:49-58
61. Jenner P (2003) Oxidative stress in Parkinson's disease. Ann Neurol 53(Suppl 3):S26-S36
62. Junn E, Mouradian M (2001) Apoptotic signaling in dopamine-induced cell death: the role of oxidative stress, p38 mitogen activated protein kinase, cytochrome c and caspases. J Neurochem 78:374-383
63. Keeny P, Xie J, Capaldi R, Bennett J Jr (2006) Parkinson's disease brain mitochondrial complex I has oxidatively damaged subunits, is functionally impaired and misassembled. J Neurosci Res 26:5256-5264
64. Kim R, Peters M, Jang Y, Shi W, Pintilie M, Fletcher G, DeLuca C, Liepa J, Zhou L, Snow B, Binari R, Manoukian A, Bray M, Liu F, Tsao M, Mak T (2005) DJ-1, a novel regulator of the tumor suppressor PTEN. Cancer Cell 7:263-273
65. Kim S, Kong P, Kim B, Sheen D, Nam S, Chun W (2004) Inhibitory action of minocycline on lipopolysaccharide-induced release of nitric oxide and prostaglandin E2 in BV2 microglial cells. Arch Pharm Res 27:314-318
66. Kitamura Y, Kosaka T, Kakimura J, Matsouka Y, Nomura Y, Tan-guchi T (1998) Protective effects of the antiparkinsonian drugs talipexole and pramipexole against 1-methyl 4-phenylpyridinium-induced apoptotic death in human neuroblastoma SH-SY5Y cells. Mol Pharmacol 54:1046-1054
67. Kraytsberg Y, Kudryavtseva E, McKee A, Geula C, Kowall N, Khrapko K (2006) Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons. Nat Genet 38:507-508
68. Kulich S, Chu C (2003) Role of reactive oxygen species in ERK phosphorylation and 6-hydroxydopamine cytotoxicity. J Biosci 28:83-89
69. Kulich S, Chu C (2001) Sustained extracellular signal-regulated kinase activation by 6-hydroxydopamine: implications for Parkinson's disease. J Neurochem 77:1058-1066
70. Kulisz A, Chen N, Chandel N, Shao Z, Schumacker P (2002) Mitochondrial ROS initiate phosphorylation of p38 MAP kinase during hypoxia in cardiomyocytes. Am J Physiol Lung Cell Mol Physiol 282:L1324-L1329
71. Kuroda Y, Mitsui T, Kunishige M, Matsumoto T (2006) Parkin enhances mitochondrial biogenesis in proliferating cells. Hum Mol Genet 15:883-895
72. Langston J, Ballard P, Tetrud J, Irwin I (1983) Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219:979-980
73. Le W, Rowe D, Xie W, Ortiz I, He Y, Appel S (2001) Microglial activation and dopaminergic cell injury: an in vitro model relevant to Parkinson's disease. J Neurosci Res 21:8447-8455
74. Liberatore G, Jackson-Lewis V, Vukosavic S, Mandir A, Vila M, McAuliffe W, Dawson V, Dawson T, Przedborski S (1999) Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson's. Nat Med 5:1403-1409
75. Lin M, Beal M (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787-795
76. Lindersson E, Beedholms R, Hojrup P, Moos T, Gai W, Gendil K, Jensen P (2004) Proteasomal inhibition by α-synuclein filaments and oligomers. J Biol Chem 279:12924-12934
77. Liu B, Gao H, Wang J, Jeohn GH, Cooper CL, Hong JS (2002) Role of nitric oxide in inflammation-mediated neurodegeneration. Ann NY Acad Sci 991:80-92
78. Liu B, Jiang J, Wilson B, Du L, Yang S, Wang JY, Wu G, Cao X, Hong J (2000) Systemic infusion of naloxone reduces degeneration of rat substantia nigral dopaminergic neurons induced by intranigral injection of lipopolysaccharide. J Pharmacol Exp Ther 295:125-132
79. Liu Y, Qin L, Li G, Zhang W, An L, Liu B (2003) Dextromethorplan protects dopaminergic neurons against inflammation-mediated degeneration through inhibition of microglial activation. J Pharmacol Exp Ther 305:212-218
80. Lu X, Bing G, Hagg T (2000) Naloxone prevents microglia-induced degeneration of dopaminergic substantia nigra neurons in adult rats. Neuroscience 97:285-291
81. Ma J, Ma J (2002) The dual effect of the particulate and organic components of diesel exhaust particles on the alteration of pulmonary immune/inflammatory responses and metabolic enzymes. J Environ Carcinog Ecotoxicol Rev 20:117-147
82. Maguire-Zeiss K, Federoff H (2003) Convergent pathobiologic model of Parkinson's disease. Ann NY Acad Sci 991:152-166
83. McGeer P, Yasojima K, McGeer E (2001) Inflammation in Parkinson's disease. Adv Neurol 86:83-89
84. Menzies F, Yenisetti S, Min K-T (2005) Roles of Drosophila DJ-1 in survival of dopaminergic neurons and oxidative stress. Curr Biol 15:1578-1582
85. Meulener M, Whitworth AJ, Armstrong-Gold C, Rizzu P, Heutink P, Wes P, Pallanck L, Bonini N (2005) Drosophila DJ-1 mutants are selectively sensitive to environmental toxins associated with Parkinson's disease. Curr Biol 15:1572-1577
86. Minghetti L, Levi G (1998) Microglia as effector cells in brain damage and repair: focus on prostanoids and nitric oxide. Prog Neurobiol 54:99-125
87. Moore D, West A, Dawson V, Dawson T (2005) Molecular pathophysiology of Parkinson's disease. Annu Rev Neurosci 28:57-87
88. Nagatsu T, Mogi M, Ichinose H, Togari A (2000) Changes in cytokines and neurotrophins in Parkinson's disease. J Neural Transm Suppl 60:277-290
89. Nemoto S, Takeda K, Yu Z, Ferrans V, Finkel T (2000) Role for mitochondrial oxidants as regulators of cellular metabolism. Mol Cell Biol 20:7311-7318
90. Niehaus I (2004) Lipopolysaccharides induce inflammation-mediated neurodegeneration in the substantia nigra and cerebral cortex (a case report). In: Hanin I, Cacabelos R (eds) New trends in Alzheimer and Parkinson related disorders. Monduzzi Editore, Bologna, pp 36-39
91. Olanow C, McNaught K (2006) Ubiquitin-proteasome system and Parkinson's disease. Mov Disord 21:1806-1823
92. 2 induced apoptotic death. Neurobiol Dis 20:141-154
93. 2-terminal kinase signaling cascades is required for induction of apoptosis in Parkinson's disease cybrids. Mol Cell Neurosci 28(3):452-461
94. Park J, Lee S, Lee S, Kim Y, Song S, Kim S, Bae E, Kim J, Shong M, Kim J, Chung J (2006) Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature 441:1157-1161
95. Parker WD Jr, Boyson SJ, Parks JK (2007) Abnormalities of the electron transport chain in idiopathic Parkinson's disease. Ann Neurol 26(6):719-723
96. Perier C, Bove J, Wu DC, Dehay B, Choi DK, Jackson-Lewis V, Rathke-Hartlieb S, Bouillet P, Strasser A, Schulz JB, Przedborski S, Vila M (2007) Two molecular pathways initiate mitochondria-dependent dopaminergic neurodegeneration in experimental Parkinson's disease. Proc Natl Acad Sci USA 104:8161-8166
97. Petit A, Kawarai T, Paitel E, Sanjo N, Maj M, Scheid M, Chen F, Gu Y, Hasegawa H, Salehi-Rad S, Wang L, Rogaeva E, Fraser P, Robinson B, St George-Hyslop P, Tandon A (2005) Wild-type PINK1 prevents basal and induced neuronal apoptosis, a protective effect abrogated by Parkinson disease-related mutations. J Biol Chem 280:34025-34032
98. Petrovitch H, Ross GW, Abbott R, Sanderson W, Sharp D, Tanner C, Masaki K, Blanchette P, Popper J, Foley D, Launer L, White L (2002) Plantation work and risk of Parkinson disease in a population-based longitudinal study. Arch Neurol 59:1787-1792
99. Schapira A (2006) Etiology of Parkinson's disease. Neurology 66:S10-S23
100. Schapira A (2006) Mitochondrial disease. Lancet 368:70-82
101. Schapira A, Cooper JM, Dexter D, Clark JB, Jenner P, Marsden CD (1990) Mitochondrial complex I deficiency in Parkinson's disease. J Neurochem 54:823-827
102. Shen J, Cookson M (2004) Mitochondria and dopamine: new insights into recessive parkinsonism. Neuron 43:301-304
103. Sherer T, Betarbet R, Greenamyre J (2002) Environment, mitochondria, and Parkinson's disease. Neuroscientist 8:192-197
104. Sherer T, Betarbet R, Stout AK, Lund S, Baptista M, Panov A, Cookson M, Greenamyre J (2002) An in vitro model of Parkinson's disease: linking mitochondrial impairment to altered alpha-synuclein metabolism and oxidative damage. J Neurosci 22:7006-7015
105. Sian J, Dexter D, Jenner P, Marsden C (1991) Decreased in nigral glutathione in Parkinson's disease. Br J Pharmacol 104:281
106. Siciliano G, Mancuso M, Ceravolo R, Lombardi V, Iudice A, Bonuccelli U (2001) Mitochondrial DNA rearrangements in young onset parkinsonism: two case reports. J Neurol Neurosurg Psychiat 71:685-687
107. Silvestri L, Caputo V, Bellacchio E, Atorino L, Dallapiccola B, Valente E, Casari G (2005) Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism. Hum Mol Genet 14:3477-3492
108. Singh M, Patel S, Dikshit M, Gupta Y (2006) Contribution of genomics and proteomics in understanding the role of modifying factors in Parkinson's disease. Indian J Biochem Biophys 43:69-81
109. Smeyne R, Jackson-Lewis V (2005) The MPTP model of Parkinson's disease. Brain Res Mol Brain Res 134:57-66
110. Smigrodzki R, Parks J, Parker W (2004) High frequency of mitochondrial complex I mutations in Parkinson's disease and aging. Neurobiol Aging 25:1273-1281
111. Song D, Shults C, Sisk A, Rockenstein E, Masliah E (2004) Enhanced substantia nigra mitochondrial pathology in human α-synuclein transgenic mice after treatment with MPTP. Exp Neurol 186:158-172
112. Sriram K, Matheson J, Benkovic S, Miller D, Luster M, O'Callaghan J (2002) Mice deficient in TNF receptors are protected against dopaminergic neurotoxicity: implications for Parkinson's disease. FASEB J 16:474-476
113. Strauss K, Martins L, Plun-Favreau H, Marx F, Kautzmann S, Berg D, Gasser T, Wszolek Z, Muller T, Bornemann A, Wolburg H, Downward J, Riess O, Schulz J, Kruger R (2005) Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease. Hum Mol Genet 14:2099-2111
114. Sulzer D, Zecca L (2000) Intraneuronal dopamine-quinone synthesis: a review. Neurotox Res 1:181-195
115. Suzuki Y, Imai Y, Nakayama H, Takahashi K, Takio K, Takahashi R (2001) A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death. Mol cell Neurosci 8:613-621
116. Swerdlow RH, Parks JK, Miller SW, Tuttle JB, Trimmer PA, Sheehan JP, Bennett JP Jr, Davis RE, Parker WD Jr (1996) Origin and functional consequences of the complex I defect in Parkinson's disease. Ann Neurol 40(4):663-671
117. Takai N, Nakanishi H, Tanabe K, Nishioku T, Sugiyama T, Fujiwara M, Yamamoto K (1998) Involvement of caspase-like pin apoptosis of neural PC12 cells and primary cultures microglia induced by 6-hydroxydopamine. J Neurosci Res 54:214-222
118. Teismann P, Tieu K, Cohen O, Choi D, Wu D, Marks D, Vila M, Jackson-Lewis V, Przedborski S (2003) Pathologic role of glial cells in Parkinson's disease. Movement Dis 18:121-129
119. Teismann P, Vila M, Choi D, Tieu K, Wu D, Jackson-Lewis V, Przedborski S (2003) Cylooxygenase-2 is instrumental in Parkinson's disease neurodegeneration. Proc Natl Acad Sci USA 100:5473-5478
120. Thyagarajan D, Bressman S, Bruno C, Przedborski S, Shanske S, Lynch T, Fahn S, DiMauro S (2000) A novel mitochondrial 12S rRNA point mutation in Parkinsonism, deafness and neuropathy. Ann Neurol 48:730-736
121. Trifunovic A, Hansson A, Wredenberg A, Rovio A, Dufour E, Khvorostov I, Spelbrink J, Wibom R, Jacobs H, Larsson N (2005) Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production. Proc Natl Acad Sci USA 102:17993-17998
122. Trimmer PA, Borland MK, Keeney PM, Bennett JP Jr, Parker WD Jr (2004) Parkinson's disease transgenic mitochondrial cybrids generate Lewy inclusion bodies. J Neurochem 88(4):800-812
123. van der Walt J, Nicodemus K, Martin E, Scott W, Nance M, Watts R, Hubble J, Haines J, Koller W, Lyons K, Pahwa R, Stern M, Colcher A, Hiner B, Jankovic J, Ondo W, Allen FJ, Goetz C, Small G, Mastaglia F, Stajich J, McLaurin A, Middleton L, Scott B, Schmechel D, Pericak-Vance M, Vance J (2003) Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease. Am J Hum Genet 72:804-811
124. Vijitruth R, Liu M, Choi D, Nguyen X, Hunter R, Bing G (2006) Cyclooxygenase-2 mediates microglial activation and secondary dopaminergic cell death in the mouse MPTP model of Parkinson's disease. J Neuroinflammation 3:1742-2094
125. von Bohlen und Halbach O, Schober A, Krieglstein K (2004) Genes, proteins, and neurotoxins involved in Parkinson's disease. Prog Neurobiol 73:151-177
126. Waragai M, Wei J, Fujita M, Nakai M, Ho G, Masliah E, Akatsu H, Yamada T, Hashimoto M (2006) Increased level of DJ-1 in the cerebrospinal fluids of sporadic Parkinson's disease. Biochem Biophys Res Commun 345(3):967-972
127. Welty-Wolf K, Simonson S, Huang Y, Fracica P, Patterson J, Piantadosi C (1996) Ultrastructural changes in skeletal muscle mitochondria in Gram-negative sepsis. Shock 5:378-384
128. West A, Moore D, Biskup S, Bugayenko A, Smith W, Ross C, Dawson V, Dawson T (2005) Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci USA 102:16842-16847
129. Wood-Kaczmar A, Gandhi S, Wood N (2006) Understanding the molecular causes of Parkinson's disease. Trends Mol Med 12:521-528
130. Wu D, Teismann P, Tieu K, Vila M, Jackson-Lewis V, Ischiropoulos H, Przedborski S (2003) NADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. Proc Natl Acad Sci USA 100:6145-6150
131. Xie Z, Smith C, Van Eldik L (2004) Activated glia induce neuron death via MAP kinase signaling pathways involving JNK and p38. Glia 45:170-179
132. Yoritaka A, Hattori N, Uchida K, Tanaka M, Stadtman E, Mizuno Y (1996) Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease. Proc Natl Acad Sci USA 93:2696-2701
133. Zhang J, Stanton D, Nguyen X, Liu M, Zhang Z, Gash D, Bing G (2005) Intrapallidal lipopolysaccharide injection increases iron and ferritin levels in glia of the rat substantia nigra and induces locomotor deficits. Neuroscience 135:829-838
134. Zhu J-H, Guo F, Shelburne J, Watkins S, Chu C (2003) Localization of phosphorylated ERK/MAP kinases to mitochondria and autophagosomes in Lewy body diseases. Brain Pathol 13:473-481
135. Zhu J-H, Kulich S, Oury T, Chu C (2002) Cytoplasmic aggregates of phosphorylated extracellular signal-regulated kinase in Lewy body diseases. Am J Pathol 161:2087-2098