Genetic findings in Parkinson's disease and translation into treatment: A leading role for mitochondria?

Genes, Brain and Behavior

Volumn 7, Issue 2, 2008, Pages 129-151

  Bogaerts, V ^a,b,c   Theuns, J ^a,b,c   Van Broeckhoven, C ^a,b,c  

^a DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

^b UNIVERSITY OF ANTWERP   (Belgium)

^c UNIVERSITY OF ANTWERP   (Belgium)

Author keywords

Genetics; Mitochondria; Neuroprotection; Nuclear encoded proteins; Oxidative stress; Parkinson's disease; Treatment

Indexed keywords

ALPHA SYNUCLEIN; DJ 1 PROTEIN; LEUCINE RICH REPEAT KINASE 2; NUCLEAR PROTEIN; PARKIN; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; SERINE PROTEINASE OMI;

DEGENERATIVE DISEASE; DISEASE COURSE; DISORDERS OF MITOCHONDRIAL FUNCTIONS; FAMILIAL DISEASE; GENETIC ANALYSIS; HUMAN; MOLECULAR GENETICS; NEUROPROTECTION; OXIDATIVE STRESS; PARKINSON DISEASE; PATHOGENESIS; PRIORITY JOURNAL; REVIEW;

1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; APOPTOSIS; DISEASE PROGRESSION; ENZYMES; HUMANS; MITOCHONDRIA; OXIDATIVE STRESS; PARKINSON DISEASE; UBIQUITIN-PROTEIN LIGASES;

ANIMALIA;

EID: 40349085926     PISSN: 16011848     EISSN: 1601183X     Source Type: Journal    
DOI: 10.1111/j.1601-183X.2007.00342.x     Document Type: Review

References (286)

1. Abeliovich, A., Schmitz, Y., Farinas, I., Choi-Lundberg, D., Ho, W.H., Castillo, P.E., Shinsky, N., Verdugo, J.M.G., Armanini, M., Ryan, A., Hynes, M., Phillips, H., Sulzer, D. Rosenthal, A 2000) Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 25, 239 252.
2. Abou-Sleiman, P.M., Healy, D.G., Quinn, N., Lees, A.J. Wood, N.W 2003) The role of pathogenic DJ-1 mutations in Parkinson's disease. Ann Neurol 54, 283 286.
3. Abou-Sleiman, P.M., Healy, D.G. Wood, N.W 2004) Causes of Parkinson's disease: genetics of DJ-1. Cell Tissue Res 318, 185 188.
4. Abou-Sleiman, P.M., Muqit, M.M.K., McDonald, N.Q., Yang, Y.X., Gandhi, S., Healy, D.G., Harvey, K., Harvey, R.J., Deas, E., Hatia, K., Quinn, N., Lees, A., Latchman, D.S. Wood, N.W 2006) A heterozygous effect for PINK1 mutations in Parkinson's disease? Ann Neurol 60, 414 419.
5. Akao, Y., Maruyama, W., Yi, H., Shamoto-Nagai, M., Youdim, M.B.H. Naoi, M 2002) An anti-Parkinson's disease drug, N-propargyl-1(R)-aminoindan (rasagiline), enhances expression of anti-apoptotic Bcl-2 in human dopaminergic SH-SY5Y cells. Neurosci Lett 326, 105 108.
6. Andres, R.H., Huber, A.W., Schlattner, U., Perez-Bouza, A., Krebs, S.H., Seiler, R.W., Wallimann, T. Widmer, H.R 2005) Effects of creatine treatment on the survival of dopaminergic neurons in cultured fetal ventral mesencephalic tissue. Neuroscience 133, 701 713.
7. Andringa, G., Eshuis, S., Perentes, E., Maguire, R.P., Roth, D., Ibrahim, M., Leenders, K.L. Cools, A.R 2003) TCH346 prevents motor symptoms and loss of striatal FDOPA uptake in bilaterally MPTP-treated primates. Neurobiol Dis 14, 205 217.
8. Autere, J., Moilanen, J.S., Finnila, S., Soininen, H., Mannermaa, A., Hartikainen, P., Hallikainen, M. Majamaa, K 2004) Mitochondrial DNA polymorphisms as risk factors for Parkinson's disease and Parkinson's disease dementia. Hum Genet 115, 29 35.
9. Beal, M.F 2003) Bioenergetic approaches for neuroprotection in Parkinson's disease. Ann Neurol 53, S39 S47.
10. Beal, M.F., Matthews, R.T., Tieleman, A. Shults, C.W 1998) Coenzyme Q(10) attenuates the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced loss of striatal dopamine and dopaminergic axons in aged. Brain Res 783, 109 114.
11. Beckman, J.S. Koppenol, W.H 1996) Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and the ugly. Am J Physiol Cell Physiol 40, C1424 C1437.
12. Behl, C 2000) Vitamin E protects neurons against oxidative cell death in vitro more effectively than 17-beta estradiol and induces the activity of the transcription factor NF-kappa B. J Neural Transm 107, 393 407.
13. Behl, C., Skutella, T., Lezoualch, F., Post, A., Widmann, M., Newton, C.J. Holsboer, F 1997) Neuroprotection against oxidative stress by estrogens: structure-activity relationship. Mol Pharmacol 51, 535 541.
14. Ben Shachar, D., Eshel, G., Finberg, J.P. Youdim, M.B 1991) The iron chelator desferrioxamine (Desferal) retards 6-hydroxydopamine-induced degeneration of nigrostriatal dopamine neurons. J Neurochem 56, 1441 1444.
15. Ben Shachar, D., Kahana, N., Kampel, V., Warshawsky, A. Youdim, M.B.H 2004) Neuroprotection by a novel brain permeable iron chelator, VK-28, against 6-hydroxydopamine lesion in rats. Neuropharmacology 46, 254 263.
16. Bender, A., Koch, W., Elstner, M., Schombacher, Y., Bender, J., Moeschl, M., Gekeler, F., Muller-Myhsok, B., Gasser, T., Tatsch, K. Klopstock, T 2006a) Creatine supplementation in Parkinson disease: a placebo-controlled randomized pilot trial. Neurology 67, 1262 1264.
17. Bender, A., Krishnan, K.J., Morris, C.M., Taylor, G.A., Reeve, A.K., Perry, R.H., Jaros, E., Hersheson, J.S., Betts, J., Klopstock, T., Taylor, R.W. Turnbull, D.M 2006b) High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet 38, 515 517.
18. Berg, D., Schweitzer, K., Leitner, P., Zimprich, A., Lichtner, P., Belcredi, P., Brussel, T., Schulte, C., Maass, S. Nagele, T 2005) Type and frequency of mutations in the LRRK2 gene in familial and sporadic Parkinson's disease*. Brain 128, 3000 3011.
19. Betarbet, R., Sherer, T.B., MacKenzie, G., Garcia-Osuna, M., Panov, A.V. Greenamyre, J.T 2000) Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci 3, 1301 1306.
20. Bhakar, A.L., Howell, J.L., Paul, C.E., Salehi, A.H., Becker, E.B.E., Said, F., Bonni, A. Barker, P.A 2003) Apoptosis induced by p75NTR overexpression requires jun kinase-dependent phosphorylation of bad. J Neurosci 23, 11373 11381.
21. Bharath, S., Hsu, M., Kaur, D., Rajagopalan, S. Andersen, J.K 2002) Glutathione, iron and Parkinson's disease. Biochem Pharmacol 64, 1037 1048.
22. Birkmayer, W., Knoll, J., Riederer, P., Youdim, M.B.H., Hars, V. Marton, J 1985) Increased life expectancy resulting from addition of L-deprenyl to madopar treatment in Parkinson's-disease - a longterm study. J Neural Transm 64, 113 127.
23. Birkmayer, W., Riederer, P., Youdim, M.B.H. Linauer, W 1975) Potentiation of anti akinetic effect after L-DOPA treatment by an inhibitor of Mao-B, Deprenil. J Neural Transm 6, 303 326.
24. Bogaerts, V., Engelborghs, S., Kumar-Singh, S., Goossens, D., Pickut, B., van der Zee, J., Sleegers, K., Peeters, K., Martin, J.J., Del-Favero, J., Gasser, T., Dickson, D., Wszolek, Z., De Deyn, P., Theuns, J. Van Broeckhoven, C 2007) A novel locus for dementia with Lewy bodies: a clinically and genetically heterogeneous disorder. Brain, doi: 10.1093.
25. Bonifati, V., Rizzu, P., van Baren, M.J., Schaap, O., Breedveld, G.J., Krieger, E., Dekker, M.C., Squitieri, F., Ibanez, P., Joosse, M., van Dongen, J.W., Vanacore, N., van Swieten, J.C., Brice, A., Meco, G., van Duijn, C.M., Oostra, B.A. Heutink, P 2003) Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299, 256 259.
26. Braak, H., Ghebremedhin, E., Rub, U., Bratzke, H. Del Tredici, K 2004) Stages in the development of Parkinson's disease-related pathology. Cell Tissue Res 318, 121 134.
27. Bredesen, D.E., Rao, R.V. Mehlen, P 2006) Cell death in the nervous system. Nature 443, 796 802.
28. Brown, G.C. Borutaite, V 2002) Nitric oxide inhibition of mitochondrial respiration and its role in cell death. Free Radic Biol Med 33, 1440 1450.
29. Burton, G.W., Joyce, A. Ingold, K.U 1983) Is vitamin-e the only lipid-soluble, chain-breaking antioxidant in human-blood plasma and erythrocyte-membranes. Arch Biochem Biophys 221, 281 290.
30. Cabin, D.E., Shimazu, K., Murphy, D., Cole, N.B., Gottschalk, W., McIlwain, K.L., Orrison, B., Chen, A., Ellis, C.E., Paylor, R., Lu, B. Nussbaum, R.L 2002) Synaptic vesicle depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking alpha-synuclein. J Neurosci 22, 8797 8807.
31. Callier, S., Morissette, M., Grandbois, M. Di Paolo, T 2000) Stereospecific prevention by 17 beta-estradiol of MPTP-induced dopamine depletion in mice. Synapse 37, 245 251.
32. Canet-Aviles, R.M., Wilson, M.A., Miller, D.W., Ahmad, R., McLendon, C., Bandyopadhyay, S., Baptista, M.J., Ringe, D., Petsko, G.A. Cookson, M.R 2004) The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization. Proc Natl Acad Sci U S A 101, 9103 9108.
33. Casarejos, M.J., Menendez, J., Solano, R.M., Rodriguez-Navarro, J.A., Garcia de Yebenes, J. Mena, M.A 2006) Susceptibility to rotenone is increased in neurons from parkin null mice and is reduced by minocycline. J Neurochem 97, 934 946.
34. Cassarino, D.S., Fall, C.P., Smith, T.S. Bennett, J.P 1998) Pramipexole reduces reactive oxygen species production in vivo and in vitro and inhibits the mitochondrial permeability transition produced by the Parkinsonian neurotoxin methylpyridinium ion. J Neurochem 71, 295 301.
35. Cha, G.H., Kim, S., Park, J., Lee, E., Kim, M., Lee, S.B., Kim, J.M., Chung, J. Cho, K.S 2005) Parkin negatively regulates JNK pathway in the dopaminergic neurons of Drosophila. Proc Natl Acad Sci U S A 102, 10345 10350.
36. Chartier-Harlin, M.C., Kachergus, J., Roumier, C., Mouroux, V., Douay, X., Lincoln, S., Levecque, C., Larvor, L., Andrieux, J., Hulihan, M., Waucquier, N., Defebvre, L., Amouyel, P., Farrer, M. Destee, A 2004) alpha-Synuclein locus duplication as a cause of familial Parkinson's disease. Lancet 364, 1167 1169.
37. Chauhan, D., Li, G.L., Hideshima, T., Podar, K., Mitsiades, C., Mitsiades, N., Munshi, N., Kharbanda, S. Anderson, K.C 2003) JNK-dependent release of mitochondrial protein, Smac, during apoptosis in multiple myeloma (MM) cells. J Biol Chem 278, 17593 17596.
38. Chen, L.N., Cagniard, B., Mathews, T., Jones, S., Koh, H.C., Ding, Y.M., Carvey, P.M., Ling, Z.D., Kang, U.J. Zhuang, X.X 2005) Age-dependent motor deficits and dopaminergic dysfunction in DJ-1 null mice. J Biol Chem 280, 21418 21426.
39. Chung, K.K., Dawson, V.L. Dawson, T.M 2005) S-nitrosylation in Parkinson's disease and related neurodegenerative disorders. Methods Enzymol 396, 139 150.
40. Ciechanover, A 1998) The ubiquitin-proteasome pathway: on protein death and cell life. EMBO J 17, 7151 7160.
41. Clark, I.E., Dodson, M.W., Jiang, C., Cao, J.H., Huh, J.R., Seol, J.H., Yoo, S.J., Hay, B.A. Guo, M 2006) Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 441, 1162 1166.
42. Clark, L.N., Afridi, S., Mejia-Santana, H., Harris, J., Louis, E.D., Cote, L.J., Andrews, H., Singleton, A., De Vrieze, F.W., Hardy, J., Mayeux, R., Fahn, S., Waters, C., Ford, B., Frucht, S., Ottman, R. Marder, K 2004) Analysis of an early-onset Parkinson's disease cohort for DJ-1 mutations. Mov Disord 19, 796 800.
43. Contestabile, A 2001) Antioxidant strategies for neurodegenerative diseases. Expert Opin Ther Pat 11, 573 585.
44. Cormier, A., Morin, C., Zini, R., Tillement, J.P. Lagrue, G 2003) Nicotine protects rat brain mitochondria against experimental injuries. Neuropharmacology 44, 642 652.
45. Cuervo, A.M., Stefanis, L., Fredenburg, R., Lansbury, P.T. Sulzer, D 2004) Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy. Science 305, 1292 1295.
46. Darios, F., Corti, O., Lucking, C.B., Hampe, C., Muriel, M.P., Abbas, N., Gu, W.J., Hirsch, E.C., 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.
47. Davis, R.J 2000) Signal transduction by the JNK group of MAP kinases. Cell 103, 239 252.
48. de Rijk, M.C., Launer, L.J., Berger, K., Breteler, M.M.B., Dartigues, J.F., Baldereschi, M., Fratiglioni, L., Lobo, A., Martinez-Lage, J., Trenkwalder, C. Hofman, A 2000) Prevalence of Parkinson's disease in Europe: a collaborative study of population-based cohorts. Neurology 54, S21 S23.
49. Dekker, M.C.J., Bonifati, V. van Duijn, C.M 2003) Parkinson's disease: piecing together a genetic jigsaw. Brain 126, 1722 1733.
50. Deng, H., Jankovic, J., Guo, Y., Xie, W. Le, W 2005) Small interfering RNA targeting the PINK1 induces apoptosis in dopaminergic cells SH-SY5Y. Biochem Biophys Res Commun 337, 1133 1138.
51. Di Fonzo, A., Rohe, C.F., Ferreira, R.J., Chien, H.F., Vacca, L., Stocchi, F., Guedes, L., Fabrizio, E., Manfredi, M., Vanacore, N., Goldwurm, S., Breedveld, G., Sampaio, C., Meco, G., Barbosa, E., Oostra, B.A. Bonifati, V 2005) A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson's disease. Lancet 365, 412 415.
52. Dickson, D.W 2007) Linking selective vulnerability to cell death mechanisms in Parkinson's disease. Am J Pathol 170, 16 19.
53. Diguet, E., Fernagut, P.O., Wei, X., Du, Y.S., Rouland, R., Gross, C., Bezard, E. Tison, F 2004) Deleterious effects of minocycline in animal models of Parkinson's disease and Huntington's disease. Eur J Neurosci 19, 3266 3276.
54. Du, C.Y., Fang, M., Li, Y.C., Li, L. Wang, X.D 2000) Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 102, 33 42.
55. Du, Y.S., Ma, Z.Z., Lin, S.Z., Dodel, R.C., Gao, F., Bales, K.R., Triarhou, L.C., Chernet, E., Perry, K.W., Nelson, D.L.G., Luecke, S., Phebus, L.A., Bymaster, F.P. Paul, S.M 2001) Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson's disease. Proc Natl Acad Sci U S A 98, 14669 14674.
56. Dykens, J.A., Moos, W.H. Howell, N 2005a) Development of 17 alpha-estradiol as a neuroprotective therapeutic agent - rationale and results from a phase I clinical study. Future Horm Ther What Basic Sci Clin Studies Teach Us 1052, 116 135.
57. Dykens, J.A., Wersinger, C. Sidhu, A 2005b) 17 beta- and 17 alpha-Estradiol are non-competitive inhibitors of dopamine uptake: implications for Parkinson's disease models and therapeutics. Drug Dev Res 66, 160 171.
58. Elm, J.J., Goetz, C.G., Ravina, B., Shannon, K., Wooten, G.F., Tanner, C.M., Palesch, Y.Y., Huang, P., Guimaraes, P., Kamp, C., Tilley, B.C. Kieburtz, K 2005) A responsive outcome for Parkinson's disease neuroprotection futility studies. Ann Neurol 57, 197 203.
59. Ernster, L. Dallner, G 1995) Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta Mol Basis Dis 1271, 195 204.
60. Eskelinen, E.L 2005) Doctor Jekyll and Mister Hyde: autophagy can promote both cell survival and cell death. Cell Death Differ 12(Suppl. 2 1468 1472.
61. Etminan, M., Gill, S.S. Samii, A 2005) Intake of vitamin E, vitamin C, and carotenoids and the risk of Parkinson's disease: a meta-analysis. Lancet Neurol 4, 362 365.
62. Faccio, L., Fusco, C., Chen, A., Martinotti, S., Bonventre, J.V. Zervos, A.S 2000) Characterization of a novel human serine protease that has extensive homology to bacterial heat shock endoprotease HtrA and is regulated by kidney ischemia. J Biol Chem 275, 2581 2588.
63. Farrer, M.J 2006) Genetics of Parkinson disease: paradigm shifts and future prospects. Nat Rev Genet 7, 306 318.
64. Fernagut, P.O. Chesselet, M.F 2004) Alpha-synuclein and transgenic mouse models. Neurobiol Dis 17, 123 130.
65. Ferraro, E. Cecconi, F 2007) Autophagic and apoptotic response to stress signals in mammalian cells. Arch Biochem Biophys 462, 210 219.
66. Fleming, S.M., Fernagut, P.O. Chesselet, M.F 2005) Genetic mouse models of parkinsonism: strengths and limitations. NeuroRx 2, 495 503.
67. Foroud, T., Uniacke, S.K., Liu, L., Pankratz, N., Rudolph, A., Halter, C., Shults, C., Marder, K., Conneally, P.M. Nichols, W.C 2003) Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease. Neurology 60, 796 801.
68. Frasier, M., Walzer, M., McCarthy, L., Magnuson, D., Lee, J.M., Haas, C., Kahle, P. Wolozin, B 2005) Tau phosphorylation increases in symptomatic mice overexpressing A30P alpha-synuclein. Exp Neurol 192, 274 287.
69. Fridovich, I 1995) Superoxide radical and superoxide dismutases. Annu Rev Biochem 64, 97 112.
70. Gal, S., Zheng, H., Fridkin, M. Youdim, M.B.H 2005) Novel multifunctional neuroprotective iron chelator-monoamine oxidase inhibitor drugs for neurodegenerative diseases. In vivo selective brain monoamine oxidase inhibition and prevention of MPTP-induced striatal dopamine depletion. J Neurochem 95, 79 88.
71. Galter, D., Westerlund, M., Carmine, A., Lindqvist, E., Sydow, O. Olson, L 2006) LRRK2 expression linked to dopamine-innervated areas. Ann Neurol 59, 714 719.
72. Gandhi, S., Muqit, M.M.K., Stanyer, L., Healy, D.G., Abou-Sleiman, P.M., Hargreaves, I., Heales, S., Ganguly, M., Parsons, L., Lees, A.J., Latchman, D.S., Holton, J.L., Wood, N.W. Revesz, T 2006) PINK1 protein in normal human brain and Parkinson's disease. Brain 129, 1720 1731.
73. Garcia-Segura, L.M., Cardona-Gomez, P., Naftolin, F. Chowen, J.A 1998) Estradiol upregulates Bcl-2 expression in adult brain neurons. Neuroreport 9, 593 597.
74. Gasser, T., Muller-Myhsok, B., Wszolek, Z.K., Oehlmann, R., Calne, D.B., Bonifati, V., Bereznai, B., Fabrizio, E., Vieregge, P. Horstmann, R.D 1998) A susceptibility locus for Parkinson's disease maps to chromosome 2p13. Nat Genet 18, 262 265.
75. George, J.M., Jin, H., Woods, W.S. Clayton, D.F 1995) Characterization of a novel protein regulated during the critical period for song learning in the Zebra finch. Neuron 15, 361 372.
76. Ghezzi, D., Marelli, C., Achilli, A., et al 2005) Mitochondrial DNA haplogroup K is associated with a lower risk of Parkinson's disease in Italians. Eur J Hum Genet 13, 748 752.
77. Gilks, W.P., Abou-Sleiman, P.M., Gandhi, S., Jain, S., Singleton, A., Lees, A.J., Shaw, K., Bhatia, K.P., Bonifati, V., Quinn, N.P., Lynch, J., Healy, D.G., Holton, J.L., Revesz, T. Wood, N.W 2005) Common LRRK2 mutation in idiopathic Parkinson's disease. Lancet 365, 415 416.
78. Glinka, Y., Tipton, K.F. Youdim, M.B.H 1996) Nature of inhibition of mitochondrial respiratory complex I by 6-hydroxydopamine. J Neurochem 66, 2004 2010.
79. Glinka, Y., Tipton, K.F. Youdim, M.B.H 1998) Mechanism of inhibition of mitochondrial respiratory complex I by 6-hydroxydopamine and its prevention by desferrioxamine. Eur J Pharmacol 351, 121 129.
80. Gloeckner, C.J., Kinkl, N., Schumacher, A., Braun, R.J., O'Neill, E., Meitinger, T., Kolch, W., Prokisch, H. Ueffing, M 2006) The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity. Hum Mol Genet 15, 223 232.
81. Goedert, M 2001) Alpha-synuclein and neurodegenerative diseases. Nat Rev Neurosci 2, 492 501.
82. Goldberg, M.S., Fleming, S.M., Palacino, J.J., Cepeda, C., Lam, H.A., Bhatnagar, A., Meloni, E.G., Wu, N., Ackerson, L.C., Klapstein, G.J., Gajendiran, M., Roth, B.L., Chesselet, M.F., Maidment, N.T., Levine, M.S. Shen, J 2003) Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons. J Biol Chem 278, 43628 43635.
83. Goldberg, M.S., Pisani, A., Haburcak, M., Vortherms, T.A., Kitada, T., Costa, C., Tong, Y., Martella, G., Tscherter, A., Martins, A., Bernardi, G., Roth, B.L., Pothos, E.N., Calabresi, P. Shen, J 2005) Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1. Neuron 45, 489 496.
84. Gong, L., Daigneault, E.A., Acuff, R.V. Kostrzewa, R.M 1991) Vitamin-E supplements fail to protect mice from acute MPTP neurotoxicity. Neuroreport 2, 544 546.
85. Gonzalez-Alegre, P 2007) Therapeutic RNA interference for neurodegenerative diseases: from promise to progress. Pharmacol Ther 114, 34 55.
86. Green, D.R. Kroemer, G 2004) The pathophysiology of mitochondrial cell death. Science 305, 626 629.
87. Greene, J.C., Whitworth, A.J., Kuo, I., Andrews, L.A., Feany, M.B. Pallanck, L.J 2003) Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc Natl Acad Sci U S A 100, 4078 4083.
88. Gu, M., Irvani, M., Cooper, J.M., King, D., Jenner, P. Schapira, A.H.V 2004) Pramipexole protects against apoptotic cell death by non-dopaminergic mechanisms. J Neurochem 91, 1075 1081.
89. Hague, S., Peuralinna, T., Eerola, J., Hellstrom, O., Tienari, P.J. Singleton, A.B 2004) Confirmation of the protective effect of iNOS in an independent cohort of Parkinson disease. Neurology 62, 635 636.
90. Hague, S., Rogaeva, E., Hernandez, D., Gulick, C., Singleton, A., Hanson, M., Johnson, J., Weiser, R., Gallardo, M., Ravina, B., Gwinn-Hardy, K., Crawley, A., George-Hyslop, P.H., Lang, A.E., Heutink, P., Bonifati, V., Hardy, J. Singleton, A 2003) Early-onset Parkinson's disease caused by a compound heterozygous DJ-1 mutation. Ann Neurol 54, 271 274.
91. Halbig, T.D., Tse, W. Olanow, C.W 2004) Neuroprotective agents in Parkinson's disease: clinical evidence and caveats. Neurol Clin 22, S1 S17.
92. Ham, J., Eilers, A., Whitfield, J., Neame, S.J. Shah, B 2000) c-Jun and the transcriptional control of neuronal apoptosis. Biochem Pharmacol 60, 1015 1021.
93. Hancock, D.B., Martin, E.R., Fujiwara, K., Stacy, M.A., Scott, B.L., Stajich, J.M., Jewett, R., Li, Y.J., Hauser, M.A., Vance, J.M. Scott, W.K 2006) NOS2A and the modulating effect of cigarette smoking in Parkinson's disease. Ann Neurol 60, 366 373.
94. Hancock, D.B., Martin, E.R., Stajich, J.M., Jewett, R., Stacy, M.A., Scott, B.L., Vance, J.M. Scott, W.K 2007) Smoking, caffeine, and nonsteroidal anti-inflammatory drugs in families with Parkinson disease. Arch Neurol 64, 576 580.
95. Hara, M.R., Agrawal, N., Kim, S.F., Cascio, M.B., Fujimuro, M., Ozeki, Y., Takahashi, M., Cheah, J.H., Tankou, S.K., Hester, L.D., Ferris, C.D., Hayward, S.D., Snyder, S.H. Sawa, A 2005) S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding. Nat Cell Biol 7, 665 U40.
96. Hara, M.R., Thomas, B., Cascio, M.B., Bae, B.I., Hester, L.D., Dawson, V.L., Dawson, T.M., Sawa, A. Snyder, S.H 2006) Neuroprotection by pharmacologic blockade of the GAPDH death cascade. Proc Natl Acad Sci U S A 103, 3887 3889.
97. Hedrich, K., Djarmati, A., Schafer, N., Hering, R., Wellenbrock, C., Weiss, P.H., Hilker, R., Vieregge, P., Ozelius, L.J., Heutink, P., Bonifati, V., Schwinger, E., Lang, A.E., Noth, J., Bressman, S.B., Pramstaller, P.P., Riess, O. Klein, C 2004a) DJ-1 (PARK7) mutations are less frequent than Parkin (PARK2) mutations in early-onset Parkinson disease. Neurology 62, 389 394.
98. Hedrich, K., Eskelson, C., Wilmot, B., Marder, K., Harris, J., Garrels, J., Meija-Santana, H., Vieregge, P., Jacobs, H., Bressman, S.B., Lang, A.E., Kann, M., Abbruzzese, G., Martinelli, P., Schwinger, E., Ozelius, L.J., Pramstaller, P.P., Klein, C. Kramer, P 2004b) Distribution, type, and origin of Parkin mutations: review and case studies. Mov Disord 19, 1146 1157.
99. Hegde, R., Srinivasula, S.M., Zhang, Z., Wassell, R., Mukattash, R., Cilenti, L., DuBois, G., Lazebnik, Y., Zervos, A.S., Fernandes-Alnemri, T. Alnemri, E.S 2002) Identification of Omi/HtrA2 as a mitochondrial apoptotic serine protease that disrupts inhibitor of apoptosis protein-caspase interaction. J Biol Chem 277, 432 438.
100. Hengartner, M.O 2000) The biochemistry of apoptosis. Nature 407, 770 776.
101. Hernan, M.A., Takkouche, B., Caamano-Isorna, F. Gestal-Otero, J.J 2002) A meta-analysis of coffee drinking, cigarette smoking, and the risk of Parkinson's disease. Ann Neurol 52, 276 284.
102. Hicks, A.A., Petursson, H., Jonsson, T., Stefansson, H., Johannsdottir, H.S., Sainz, J., Frigge, M.L., Kong, A., Gulcher, J.R., Stefansson, K. Sveinbjornsdottir, S 2002) A susceptibility gene for late-onset idiopathic Parkinson's disease. Ann Neurol 52, 549 555.
103. Holley, C.L., Olson, M.R., Colon-Ramos, D.A. Kornbluth, S 2002) Reaper eliminates IAP proteins through stimulated IAP degradation and generalized translational inhibition. Nat Cell Biol 4, 439 444.
104. Holloway, R., Shoulson, I., Kieburtz, K., et al 2000) Pramipexole vs levodopa as initial treatment for Parkinson disease - a randomized controlled trial. JAMA 284, 1931 1938.
105. Hunot, S., Vila, M., Teismann, P., Davis, R.J., Hirsch, E.C., Przedborski, S., Rakic, P. Flavell, R.A 2004) JNK-mediated induction of cyclooxygenase 2 is required for neurodegeneration in a mouse model of Parkinson's disease. Proc Natl Acad Sci U S A 101, 665 670.
106. Ibanez, P., Bonnet, A.M., Debarges, B., Lohmann, E., Tison, F., Pollak, P., Agid, Y., Durr, A. Brice, A 2004) Causal relation between alpha-synuclein gene duplication and familial Parkinson's disease. Lancet 364, 1169 1171.
107. Iida, M., Miyazaki, I., Tanaka, K., Kabuto, H., Iwata-Ichikawa, E. Ogawa, N 1999) Dopamine D2 receptor-mediated antioxidant and neuroprotective effects of ropinirole, a dopamine agonist. Brain Res 838, 51 59.
108. Iravani, M.M., Haddon, C.O., Cooper, J.M., Jenner, P. Schapira, A.H 2006) Pramipexole protects against MPTP toxicity in non-human primates. J Neurochem 96, 1315 1321.
109. Ishitani, R., Kimura, M., Sunaga, K., Katsube, N., Tanaka, M. Chuang, D.M 1996) An antisense oligodeoxynucleotide to glyceraldehyde-3-phosphate dehydrogenase blocks age-induced apoptosis of mature cerebrocortical neurons in culture. J Pharmacol Exp Ther 278, 447 454.
110. Itier, J.M., Ibanez, P., Mena, M.A., et al 2003) Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse. Hum Mol Genet 12, 2277 2291.
111. Jiang, H., Luan, Z., Wang, J. Xie, J 2006) Neuroprotective effects of iron chelator Desferal on dopaminergic neurons in the substantia nigra of rats with iron-overload. Neurochem Int 49, 605 609.
112. Jiang, H.B., Ren, Y., Zhao, J.H. Feng, J 2004) Parkin protects human dopaminergic neuroblastoma cells against dopamine-induced apoptosis. Hum Mol Genet 13, 1745 1754.
113. Jones, J.M., Datta, P., Srinivasula, S.M., Ji, W., Gupta, S., Zhang, Z., Davies, E., Hajnoczky, G., Saunders, T.L., Van Keuren, M.L., Fernandes-Alnemri, T., Meisler, M.H. Alnemri, E.S 2003) Loss of Omi mitochondrial protease activity causes the neuromuscular disorder of mnd2 mutant mice. Nature 425, 721 727.
114. Joo, W.S., Jin, B.K., Park, C.W., Maeng, S.H. Kim, Y.S 1998) Melatonin increases striatal dopaminergic function in 6-OHDA-lesioned rats. Neuroreport 9, 4123 4126.
115. Junghanns, S., Glockler, T. Reichmann, H 2004) Switching and combining of dopamine agonists. J Neurol 251, 19 23.
116. Kalivendi, S.V., Cunningham, S., Kotamraju, S., Joseph, J., Hillard, C.J. Kalyanaraman, B 2004) alpha-Synuclein up-regulation and aggregation during MPP+-induced apoptosis in neuroblastoma cells - intermediacy of transferrin receptor iron and hydrogen peroxide. J Biol Chem 279, 15240 15247.
117. Kang, S.J., Scott, W.K., Li, Y.J., Hauser, M.A., van der Walt, J.M., Fujiwara, K., Mayhew, G.M., West, S.G., Vance, J.M. Martin, E.R 2006) Family-based case-control study of MAOA and MAOB polymorphisms in Parkinson disease. Mov Disord 21, 2175 2180.
118. Kerr, J.F., Wyllie, A.H. Currie, A.R 1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26, 239 257.
119. Khan, N.L., Jain, S., Lynch, J.M., et al 2005) Mutations in the gene LRRK2 encoding dardarin (PARK8) cause familial Parkinson's disease: clinical, pathological, olfactory and functional imaging and genetic data. Brain 128, 2786 2796.
120. Khan, N.L., Valente, E.M., Bentivoglio, A.R., Wood, N.W., Albanese, A., Brooks, D.J. Piccini, P 2002) Clinical and subclinical dopaminergic dysfunction in PARK6-linked parkinsonism: an F-18-dopa PET study. Ann Neurol 52, 849 853.
121. Khwaja, M., McCormack, A., McIntosh, J.M., Di Monte, D.A. Quik, M 2007) Nicotine partially protects against paraquat-induced nigrostriatal damage in mice; link to alpha6beta2* nAChRs. J Neurochem 100, 180 190.
122. Kienzl, E., Puchinger, L., Jellinger, K., Linert, W., Stachelberger, H. Jameson, R.F 1995) The role of transition metals in the pathogenesis of Parkinson's disease. J Neurol Sci 134, 69 78.
123. Kim, R.H., Smith, P.D., Aleyasin, H., Hayley, S., Mount, M.P., Pownall, S., Wakeham, A., You, T., Kalia, S.K., Horne, P., Westaway, D., Lozano, A.M., Anisman, H., Park, D.S. Mak, T.W 2005) Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress. Proc Natl Acad Sci U S A 102, 5215 5220.
124. King, D.F., Cooper, J.M. Schapira, A.H.V 2001) Pramipexole protects against MPP+ toxicity in SHSY5Y cells by maintaining mitochondrial membrane potential. Neurology 56, A377 A378.
125. Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., Yokochi, M., Mizuno, Y. Shimizu, N 1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392, 605 608.
126. Kitamura, Y., Kosaka, T., Kakimura, J.I., Matsuoka, Y., Kohno, Y., Nomura, Y. Taniguchi, 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.
127. Klein, C 2006) Implications of genetics on the diagnosis and care of patients with Parkinson disease. Arch Neurol 63, 328 334.
128. Kostrzewa, R.M 2000) Review of apoptosis vs. necrosis of substantia nigra pars compacta in Parkinson's disease. Neurotoxicol Res 2, 239 250.
129. Kraytsberg, Y., Kudryavtseva, E., McKee, A.C., Geula, C., Kowall, N.W. Khrapko, K 2006) Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons. Nat Genet 38, 518 520.
130. Krueger, M.J., Singer, T.P., Casida, J.E. Ramsay, R.R 1990) Evidence that the blockade of mitochondrial respiration by the neurotoxin 1-methyl-4-phenylpyridinium (Mpp+) involves binding at the same site as the respiratory inhibitor, rotenone. Biochem Biophys Res Commun 169, 123 128.
131. Kruger, R., Kuhn, W., Muller, T., Woitalla, D., Graeber, M., Kosel, S., Przuntek, H., Epplen, J.T., Schols, L. Riess, O 1998) Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nat Genet 18, 106 108.
132. Kupsch, A., Sautter, J., Gotz, M.E., Breithaupt, W., Schwarz, J., Youdim, M.B.H., Riederer, P., Gerlach, M. Oertel, W.H 2001) Monoamine oxidase-inhibition and MPTP-induced neurotoxicity in the non-human primate: comparison of rasagiline (TVP 1012) with selegiline. J Neural Transm 108, 985 1009.
133. Kuroda, Y., Mitsui, T., Kunishige, M., Shono, M., Akaike, M., Azuma, H. Matsumoto, T 2006) Parkin enhances mitochondrial biogenesis in proliferating cells. Hum Mol Genet 15, 883 895.
134. Lan, J. Jiang, D.H 1997) Desferrioxamine and vitamin E protect against iron and MPTP-induced neurodegeneration in mice. J Neural Transm 104, 469 481.
135. Langston, J.W., Ballard, P., Tetrud, J.W. Irwin, I 1983) Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219, 979 980.
136. Lesage, S., Magali, P., Lohmann, E., Lacomblez, L., Teive, H., Janin, S., Cousin, P.Y., Durr, A. Brice, A 2007) Deletion of the parkin and PACRG gene promoter in early-onset parkinsonism. Hum Mutat 28, 27 32.
137. Levecque, C., Elbaz, A., Clavel, J., Richard, F., Vidal, J.S., Amouyel, P., Tzourio, C., Alperovitch, A. Chartier-Harlin, M.C 2003) Association between Parkinson's disease and polymorphisms in the nNOS and iNOS genes in a community-based case - control study. Hum Mol Genet 12, 79 86.
138. Li, L.Y., Luo, L. Wang, X.D 2001) Endonuclease G is an apoptotic DNase when released from mitochondria. Nature 412, 95 99.
139. Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S.M., Ahmad, M., Alnemri, E.S. Wang, X.D 1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91, 479 489.
140. Li, W., Srinivasula, S.M., Chai, J., Li, P., Wu, J.W., Zhang, Z., Alnemri, E.S. Shi, Y 2002) Structural insights into the pro-apoptotic function of mitochondrial serine protease HtrA2/Omi. Nat Struct Biol 9, 436 441.
141. Li, Y., Tomiyama, H., Sato, K., Hatano, Y., Yoshino, H., Atsumi, M., Kitaguchi, M., Sasaki, S., Kawaguchi, S., Miyajima, H., Toda, T., Mizuno, Y. Hattori, N 2005) Clinicogenetic study of PINK1 mutations in autosomal recessive early-onset parkinsonism. Neurology 64, 1955 1957.
142. Li, Y.J., Scott, W.K., Zhang, L., Lin, P.I., Oliveira, S.A., Skelly, T., Doraiswamy, M.P., Welsh-Bohmer, K.A., Martin, E.R., Haines, J.L., Pericak-Vance, M.A. Vance, J.M 2006) Revealing the role of glutathione S-transferase omega in age-at-onset of Alzheimer and Parkinson diseases. Neurobiol Aging 27, 1087 1093.
143. Linert, W., Bridge, M.H., Huber, M., Bjugstad, K.B., Grossman, S. Arendash, G.W 1999) In vitro and in vivo studies investigating possible antioxidant actions of nicotine: relevance to Parkinson's and Alzheimer's diseases. Biochim Biophys Acta Mol Basis Dis 1454, 143 152.
144. Liochev, S.I. Fridovich, I 1994) The role of O-2-center-dot- in the production of ho-center-dot - in-vitro and in-vivo. Free Radic Biol Med 16, 29 33.
145. Litvan, I., Chesselet, M.F., Gasser, T., Di Monte, D.A., Parker, D., Jr., Hagg, T., Hardy, J., Jenner, P., Myers, R.H., Price, D., Hallett, M., Langston, W.J., Lang, A.E., Halliday, G., Rocca, W., Duyckaerts, C., Dickson, D.W., Ben Shlomo, Y., Goetz, C.G. Melamed, E 2007) The etiopathogenesis of Parkinson disease and suggestions for future research. Part II. J Neuropathol Exp Neurol 66, 329 336.
146. Lockhart, P.J., Lincoln, S., Hulihan, M., Kachergus, J., Wilkes, K., Bisceglio, G., Mash, D.C. Farrer, M.J 2004) DJ-1 mutations are a rare cause of recessively inherited early onset parkinsonism mediated by loss of protein function. J Med Genet 41, 222.
147. van Loo, G., Saelens, X., van Gurp, M., MacFarlane, M., Martin, S.J. Vandenabeele, P 2002) The role of mitochondrial factors in apoptosis: a Russian roulette with more than one bullet. Cell Death Differ 9, 1031 1042.
148. Lopez-Burillo, S., Tan, D.X., Rodriguez-Gallego, V., Manchester, L.C., Mayo, J.C., Sainz, R.M. Reiter, R.J 2003) Melatonin and its derivatives cyclic 3-hydroxymelatonin, N-1-acetyl-N (2)-formyl-5-methoxykynuramine and 6-methoxymelatonin reduce oxidative DNA damage induced by Fenton reagents. J Pineal Res 34, 178 184.
149. Lotharius, J. Brundin, P 2002) Pathogenesis of Parkinson's disease: dopamine, vesicles and alpha-synuclein. Nat Rev Neurosci 3, 932 942.
150. MacLeod, D., Dowman, J., Hammond, R., Leete, T., Inoue, K. Abeliovich, A 2006) The familial parkinsonism gene LRRK2 regulates neurite process morphology. Neuron 52, 587 593.
151. Maggi, A., Ciana, P., Belcredito, S. Vegeto, E 2004) Estrogens in the nervous system: Mechanisms and nonreproductive functions. Annu Rev Physiol 66, 291 313.
152. Maker, H.S., Weiss, C., Silides, D.J. Cohen, G 1981) Coupling of dopamine oxidation (monoamine-oxidase activity) to glutathione oxidation via the generation of hydrogen-peroxide in rat-brain homogenates. J Neurochem 36, 589 593.
153. Manning-Bog, A.B. Langston, J.W 2007) Model fusion, the next phase in developing animal models for Parkinson's disease. Neurotoxicol Res 11, 219 240.
154. Mansson, R., Hansson, M.J., Morota, S., Uchino, H., Ekdahl, C.T. Elmer, E 2007) Re-evaluation of mitochondrial permeability transition as a primary neuroprotective target of minocycline. Neurobiol Dis 25, 198 205.
155. Maraganore, D.M., de Andrade, M., Elbaz, A., et al 2006) Collaborative analysis of alpha-synuclein gene promoter variability and Parkinson disease. JAMA 296, 661 670.
156. Maroney, A.C., Finn, J.P., Connors, T.J., Durkin, J.T., Angeles, T., Gessner, G., Xu, Z.H., Meyer, S.L., Savage, M.J., Greene, L.A., Scott, R.W. Vaught, J.L 2001) CEP-1347 (KT7515), a semisynthetic inhibitor of the mixed lineage kinase family. J Biol Chem 276, 25302 25308.
157. Maroney, A.C., Glicksman, M.A., Basma, A.N., Walton, K.M., Knight, E., Murphy, C.A., Bartlett, B.A., Finn, J.P., Angeles, T., Matsuda, Y., Neff, N.T. Dionne, C.A 1998) Motoneuron apoptosis is blocked by CEP-1347 (KT 7515), a novel inhibitor of the JNK signaling pathway. J Neurosci 18, 104 111.
158. Marongiu, R., Brancati, F., Antonini, A., Ialongo, T., Ceccarini, C., Scarciolla, O., Capalbo, A., Benti, R., Pezzoli, G., Dallapiccola, B., Goldwurm, S. Valente, E.M 2007) Whole gene deletion and splicing mutations expand the PINK1 genotypic spectrum. Hum Mutat, Mutation in Brief 943 online.
159. Martin, L.J., Pan, Y., Price, A.C., Sterling, W., Copeland, N.G., Jenkins, N.A., Price, D.L. Lee, M.K 2006) Parkinson's disease alpha-synuclein transgenic mice develop neuronal mitochondrial degeneration and cell death. J Neurosci 26, 41 50.
160. Martins, L.M., Iaccarino, I., Tenev, T., Gschmeissner, S., Totty, N.F., Lemoine, N.R., Savopoulos, J., Gray, C.W., Creasy, C.L., Dingwall, C. Downward, J 2002) The serine protease Omi/HtrA2 regulates apoptosis by binding XIAP through a reaper-like motif. J Biol Chem 277, 439 444.
161. Martins, L.M., Morrison, A., Klupsch, K., Fedele, V., Moisoi, N., Teismann, P., Abuin, A., Grau, E., Geppert, M., Livi, G.P., Creasy, C.L., Martin, A., Hargreaves, I., Heales, S.J., Okada, H., Brandner, S., Schulz, J.B., Mak, T. Downward, J 2004) Neuroprotective role of the Reaper-related serine protease HtrA2/Omi revealed by targeted deletion in mice. Mol Cell Biol 24, 9848 9862.
162. Masliah, E., Rockenstein, E., Adame, A., Alford, M., Crews, L., Hashimoto, M., Seubert, P., Lee, M., Goldstein, J., Chilcote, T., Games, D. Schenk, D 2005) Effects of alpha-synuclein immunization in a mouse model of Parkinson's disease. Neuron 46, 857 868.
163. Mata, I.F., Lockhart, P.J. Farrer, M.J 2004) Parkin genetics: one model for Parkinson's disease. Hum Mol Genet 13, R127 R133.
164. Mathiasen, J.R., Mckenna, B.A.W., Saporito, M.S., Ghadge, G.D., Roos, R.P., Holskin, B.P., Wu, Z.L., Trusko, S.P., Connors, T.C., Maroney, A.C., Thomas, B.A., Thomas, J.C. Bozyczko-Coyne, D 2004) Inhibition of mixed lineage kinase 3 attenuates MPP+-induced neurotoxicity in SH-SY5Y cells. Brain Res 1003, 86 97.
165. Matthews, R.T., Ferrante, R.J., Klivenyi, P., Yang, L., Klein, A.M., Mueller, G., Kaddurah-Daouk, R. Beal, M.F 1999) Creatine and cyclocreatine attenuate MPTP neurotoxicity. Exp Neurol 157, 142 149.
166. Melrose, H.L., Lincoln, S.J., Tyndall, G.M. Farrer, M.J 2006) Parkinson's disease: a rethink of rodent models. Exp Brain Res 173, 196 204.
167. Meulener, M., Whitworth, A.J., Armstrong-Gold, C.E., Rizzu, P., Heutink, P., Wes, P.D., Pallanck, L.J. Bonini, N.M 2005) Drosophila DJ-1 mutants are selectively sensitive to environmental toxins associated with Parkinson's disease. Curr Biol 15, 1572 1577.
168. Miller, E.R., Pastor-Barriuso, R., Dalal, D., Riemersma, R.A., Appel, L.J. Guallar, E 2005) Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Int Med 142, 37 46.
169. Mitsumoto, A. Nakagawa, Y 2001) DJ-1 is an indicator for endogenous reactive oxygen species elicited by endotoxin. Free Radic Res 35, 885 893.
170. Mochizuki, H., Yamada, M. Mizuno, Y 2006) Parkin gene therapy for alpha-synucleinopathy: A rat model of Parkinson's disease. Parkinsonism Relat Disord 12, S107 S109.
171. Moosmann, B. Behl, C 1999) The antioxidant neuroprotective effects of estrogens and phenolic compounds are independent from their estrogenic properties. Proc Natl Acad Sci U S A 96, 8867 8872.
172. Nair, V.D., Olanow, C.W. Sealfon, S.C 2003) Activation of phosphoinositide 3-kinase by D-2 receptor prevents apoptosis in dopaminergic cell lines. Biochem J 373, 25 32.
173. Nichols, W.C., Pankratz, N., Hernandez, D., Paisan-Ruiz, C., Jain, S., Halter, C.A., Michaels, V.E., Reed, T., Rudolph, A., Shults, C.W., Singleton, A. Foroud, T 2005) Genetic screening for a single common LRRK2 mutation in familial Parkinson's disease. Lancet 365, 410 412.
174. Olanow, C.W., Agid, Y., Mizuno, Y., et al 2004) Levodopa in the treatment of Parkinson's disease: current controversies. Mov Disord 19, 997 1005.
175. Olanow, C.W., Hauser, R.A., Gauger, L., Malapira, T., Koller, W., Hubble, J., Bushenbark, K., Lilienfeld, D. Esterlitz, J 1995) The effect of deprenyl and levodopa on the progression of Parkinsons-disease. Ann Neurol 38, 771 777.
176. Olanow, C.W. Jankovic, J 2005) Neuroprotective therapy in Parkinson's disease and motor complications: a search for a pathogenesis-targeted, disease-modifying strategy. Mov Disord 20, S3 S10.
177. Olanow, C.W., Schapira, A.H.V., Lewitt, P.A., Kieburtz, K., Sauer, D., Olivieri, G., Pohlmann, H. Hubble, J 2006) TCH346 as a neuroprotective drug in Parkinson's disease: a double-blind, randomised, controlled trial. Lancet Neurol 5, 1013 1020.
178. Oliveira, S.A., Scott, W.K., Martin, E.R., et al 2003) Parkin mutations and susceptibility alleles in late-onset Parkinson's disease. Ann Neurol 53, 624 629.
179. Ono, K., Hirohata, M. Yamada, M 2007) Anti-fibrillogenic and fibril-destabilizing activities of anti-Parkinsonian agents for alpha-synuclein fibrils in vitro. J Neurosci Res 85, 1547 1557.
180. Orth, M. Schapira, A.H.V 2002) Mitochondrial involvement in Parkinson's disease. Neurochem Int 40, 533 541.
181. Paisan-Ruiz, C., Jain, S., Evans, E.W., et al 2004) Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 44, 595 600.
182. Palacino, J.J., Sagi, D., Goldberg, M.S., Krauss, S., Motz, C., Wacker, M., Klose, J. Shen, J 2004) Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. J Biol Chem 279, 18614 18622.
183. Pals, P., Lincoln, S., Manning, J., Heckman, M., Skipper, L., Hulihan, M., Van den, B.M., De Pooter, T., Cras, P., Crook, J., Van Broeckhoven, C. Farrer, M.J 2004) alpha-Synuclein promoter confers susceptibility to Parkinson's disease. Ann Neurol 56, 591 595.
184. Pankratz, N., Nichols, W.C., Uniacke, S.K., Halter, C., Rudolph, A., Shults, C., Conneally, P.M. Foroud, T 2003) Significant linkage of Parkinson disease to chromosome 2q36-37. Am J Hum Genet 72, 1053 1057.
185. Papadakis, E.S., Finegan, K.G., Wang, X., Robinson, A.C., Guo, C., Kayahara, M. Tournier, C 2006) The regulation of Bax by c-Jun N-terminal protein kinase (JNK) is a prerequisite to the mitochondrial-induced apoptotic pathway. FEBS Lett 580, 1320 1326.
186. Papucci, L., Schiavone, N., Witort, E., Donnini, M., Lapucci, A., Tempestini, A., Formigli, L., Zecchi-Orlandini, S., Orlandini, G., Carella, G., Brancato, R. Capaccioli, S 2003) Coenzyme Q10 prevents apoptosis by inhibiting mitochondrial depolarization independently of its free radical scavenging property. J Biol Chem 278, 28220 28228.
187. Park, J., Kim, S.Y., Cha, G.H., Lee, S.B., Kim, S. Chung, J 2005) Drosophila DJ-1 mutants show oxidative stress-sensitive locomotive dysfunction. Gene 361, 133 139.
188. Park, J., Lee, S.B., Lee, S., Kim, Y., Song, S., Kim, S., Bae, E., Kim, J., Shong, M., Kim, J.M. Chung, J 2006) Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature 441, 1157 1161.
189. Parkinson Study Group (2004a) A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease. Arch Neurol 61, 561 566.
190. Parkinson Study Group (2004b) The safety and tolerability of a mixed lineage kinase inhibitor (CEP-1347) in PD. Neurology 62, 330 332.
191. Pearce, R.K.B., Owen, A., Daniel, S., Jenner, P. Marsden, C.D 1997) Alterations in the distribution of glutathione in the substantia nigra in Parkinson's disease. J Neural Transm 104, 661 677.
192. 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., 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.
193. Polymeropoulos, M.H., Lavedan, C., Leroy, E., et al 1997) Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276, 2045 2047.
194. Priyadarshi, A., Khuder, S.A., Schaub, E.A. Priyadarshi, S.S 2001) Environmental risk factors and Parkinson's disease: a metaanalysis. Environ Res 86, 122 127.
195. Pyle, A., Foltynie, T., Tiangyou, W., Lambert, C., Keers, S.M., Allcock, L.M., Davison, J., Lewis, S.J., Perry, R.H., Barker, R., Burn, D.J. Chinnery, P.F 2005) Mitochondrial DNA haplogroup cluster UKJT reduces the risk of PD. Ann Neurol 57, 564 567.
196. Raha, S. Robinson, B.H 2000) Mitochondria, oxygen free radicals, disease and ageing. Trends Biochem Sci 25, 502 508.
197. Rajput, A., Dickson, D.W., Robinson, C.A., Ross, O.A., Dachsel, J.C., Lincoln, S.J., Cobb, S.A., Rajput, M.L. Farrer, M.J 2006) Parkinsonism, Lrrk2 G2019S, and tau neuropathology. Neurology 67, 1506 1508.
198. Ramirez, A., Heimbach, A., Gruendemann, J., Stiller, B., Hampshire, D., Cid, L.P., Goebel, I., Mubaidin, A.F., Wriekat, A.L., Roeper, J., Al Din, A., Hillmer, A.M., Karsak, M., Liss, B., Woods, C.G., Behrens, M.I. Kubisch, C 2006) Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. Nat Genet 38, 1184 1191.
199. Ramirez, A.D., Liu, X.R. Menniti, F.S 2003) Repeated estradiol treatment prevents MPTP-induced dopamine depletion in male mice. Neuroendocrinology 77, 223 231.
200. Rascol, O., Brooks, D.J., Korczyn, A.D., De Deyn, P.P., Clarke, C.E. Lang, A.E 2000) A five-year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa. N Engl J Med 342, 1484 1491.
201. Ravina, B., Kieburtz, K., Tilley, B., et al 2006) A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease. Neurology 66, 664 671.
202. Ravina, B.M., Fagan, S.C., Hart, R.G., Hovinga, C.A., Murphy, D.D., Dawson, T.M. Marler, J.R 2003) Neuroprotective agents for clinical trials in Parkinson's disease - a systematic assessment. Neurology 60, 1234 1240.
203. Reiter, R.J., Poeggeler, B., Tan, D., Chen, L.D., Manchester, L.C. Guerrero, J.M 1993) Antioxidant capacity of melatonin - a novel action not requiring a receptor. Neuroendocrinol Lett 15, 103 116.
204. Riederer, P., Sofic, E., Rausch, W.D., Schmidt, B., Reynolds, G.P., Jellinger, K. Youdim, M.B.H 1989) Transition-metals, ferritin, glutathione, and ascorbic-acid in parkinsonian brains. J Neurochem 52, 515 520.
205. Rogaeva, E., Johnson, J., Lang, A.E., et al 2004) Analysis of the PINK1 gene in a large cohort of cases with Parkinson disease. Arch Neurol 61, 1898 1904.
206. Roghani, M. Behzadi, G 2001) Neuroprotective effect of vitamin E on the early model of Parkinson's disease in rat: behavioral and histochemical evidence. Brain Res 892, 211 217.
207. Rubinsztein, D.C 2006) The roles of intracellular protein-degradation pathways in neurodegeneration. Nature 443, 780 786.
208. Sangchot, P., Sharma, S., Chetsawang, B., Porter, J., Govitrapong, P. Ebadi, M 2002) Deferoxamine attenuates iron-induced oxidative stress and prevents mitochondrial aggregation and alpha-synuclein translocation in SK-N-SH cells in culture. Dev Neurosci 24, 143 153.
209. Saporito, M.S., Brown, E.M., Miller, M.S. Carswell, S 1999) CEP-1347/KT-7515, an inhibitor of c-jun N-terminal kinase activation, attenuates the 1-methyl-4-phenyl tetrahydropyridine-mediated loss of nigrostriatal dopaminergic neurons in vivo. J Pharmacol Exp Ther 288, 421 427.
210. Sapru, M.K., Yates, J.W., Rogan, S., Jiang, L.X., Halter, J. Bohn, M.C 2006) Silencing of human alpha-synuclein in vitro and in rat brain using lentiviral-mediated RNAi. Exp Neurol 198, 382 390.
211. Saunders-Pullman, R., Gordon-Elliott, J., Parides, M., Fahn, S., Saunders, H.R. Bressman, S 1999) The effect of estrogen replacement on early Parkinson's disease. Neurology 52, 1417 1421.
212. Sawa, A., Khan, A.A., Hester, L.D. Snyder, S.H 1997) Glyceraldehyde-3- phosphate dehydrogenase: Nuclear translocation participates in neuronal and nonneuronal cell death. Proc Natl Acad Sci U S A 94, 11669 11674.
213. Sawada, H., Ibi, M., Kihara, T., Honda, K., Nakamizo, T., Kanki, R., Nakanishi, M., Sakka, N., Akaike, A. Shimohama, S 2002) Estradiol protects dopaminergic neurons in a MPP(+)Parkinson's disease model. Neuropharmacology 42, 1056 1064.
214. Schapira, A.H.V 2003) Neuroprotection in PD - a role for dopamine agonists? Neurology 61, S34 S42.
215. Schapira, A.H.V 2005) Present and future drug treatment for Parkinson's disease. J Neurol Neurosurg Psychiatry 76, 1472 1478.
216. Schapira, A.H.V., Gu, M., King, D.F., Cooper, J.M. Jenner, P 2002) Pramipexole protects against rotenone toxicity: mechanisms and implications. Neurology 58, A495 A495.
217. Schroeter, H., Boyd, C.S., Ahmed, R., Spencer, J.P.E., Duncan, R.F., Rice-Evans, C. Cadenas, E 2003) c-Jun N-terminal kinase (JNK)-mediated modulation of brain mitochondria function: new target proteins for JNK signalling in mitochondrion-dependent apoptosis. Biochem J 372, 359 369.
218. Sherer, T.B., Kim, J.H., Betarbet, R. Greenamyre, J.T 2003) Subcutaneous rotenone exposure causes highly selective dopaminergic degeneration and alpha-synuclein aggregation. Exp Neurol 179, 9 16.
219. Shimura, H., Hattori, N., Kubo, S., Mizuno, Y., Asakawa, S., Minoshima, S., Shimizu, N., Iwai, K., Chiba, T., Tanaka, K. Suzuki, T 2000) Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet 25, 302 305.
220. Shoulson, I., Fahn, S., Oakes, D., Kieburtz, K., Lang, A., Langston, J.W., LeWitt, P., Olanow, C.W., Penney, J.B., Tanner, C., Rudolph, A. Pelusio, R.M 1993) Effects of tocopherol and deprenyl on the progression of disability in early Parkinsons-disease. N Engl J Med 328, 176 183.
221. Shoulson, I., Oakes, D., Fahn, S., Lang, A., Langston, J.W., LeWitt, P., Olanow, C.W., Penney, J.B., Tanner, C., Kieburtz, K. Rudolph, A 2002) Impact of sustained deprenyl (selegiline) in levodopa-treated Parkinson's disease: a randomized placebo-controlled extension of the deprenyl and tocopherol antioxidative therapy of parkinsonism trial. Ann Neurol 51, 604 612.
222. Shoulson, I. 2006) Parkinson Study Group (PSG) & PRECEPT Investigators. CEP-1347 treatment fails to favorably modify the progression of Parkinson's disease (PRECEPT) study. Neurology 67 (1 185 185.
223. Shults, C.W., Beal, M.F., Fontaine, D., Nakano, K. Haas, R.H 1998) Absorption, tolerability, and effects on mitochondrial activity of oral coenzyme Q(10) in parkinsonian patients. Neurology 50, 793 795.
224. Shults, C.W., Haas, R.H., Passov, D. Beal, M.F 1997) Coenzyme Q(10) levels correlate with the activities of complexes I and II/III in mitochondria from parkinsonian and nonparkinsonian subjects. Ann Neurol 42, 261 264.
225. Shults, C.W., Oakes, D., Kieburtz, K., Beal, M.F., Haas, R., Plumb, S., Juncos, J.L., Nutt, J., Shoulson, I., Carter, J., Kompoliti, K., Perlmutter, J.S., Reich, S., Stern, M., Watts, R.L., Kurlan, R., Molho, E., Harrison, M. Lew, M 2002) Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol 59, 1541 1550.
226. Siderowf, A. Stern, M 2006) Clinical trials with rasagiline - evidence for short-term and long-term effects. Neurology 66, S80 S88.
227. Silvestri, L., Caputo, V., Bellacchio, E., Atorino, L., Dallapiccola, B., Valente, E.M. Casari, G 2005) Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism. Hum Mol Genet 14, 3477 3492.
228. Simon, D.K., Pulst, S.M., Sutton, J.P., Browne, S.E., Beal, M.F. Johns, D.R 1999) Familial multisystem degeneration with parkinsonism associated with the 11778 mitochondrial DNA mutation. Neurology 53, 1787 1793.
229. Singh, N., Pillay, V. Choonara, Y.E 2007) Advances in the treatment of Parkinson's disease. Prog Neurobiol 81, 29 44.
230. Singleton, A.B., Farrer, M., Johnson, J., et al 2003) alpha-Synuclein locus triplication causes Parkinson's disease. Science 302, 841.
231. Smith, W.W., Pei, Z., Jiang, H.B., Moore, D.J., Liang, Y.D., West, A.B., Dawson, V.L., Dawson, T.M. Ross, C.A 2005) Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration. Proc Natl Acad Sci U S A 102, 18676 18681.
232. Sofic, E., Paulus, W., Jellinger, K., Riederer, P. Youdim, M.B.H 1991) Selective increase of iron in substantia-nigra zona compacta of parkinsonian brains. J Neurochem 56, 978 982.
233. Sohmiya, M., Tanaka, M., Tak, N.W., Yanagisawa, M., Tanino, Y., Suzuki, Y., Okamoto, K. Yamamoto, Y 2004) Redox status of plasma coenzyme Q10 indicates elevated systemic oxidative stress in Parkinson's disease. J Neurol Sci 223, 161 166.
234. Solano, S.M., Miller, D.W., Augood, S.J., Young, A.B. Penney, J.B 2000) Expression of alpha-synuclein, parkin, and ubiquitin carboxy-terminal hydrolase L1 mRNA in human brain: Genes associated with familial Parkinson's disease. Ann Neurol 47, 201 210.
235. Spillantini, M.G., Schmidt, M.L., Lee, V.M.Y., Trojanowski, J.Q., Jakes, R. Goedert, M 1997) alpha-synuclein in Lewy bodies. Nature 388, 839 840.
236. Stokes, A.H., Hastings, T.G. Vrana, K.E 1999) Cytotoxic and genotoxic potential of dopamine. J Neurosci Res 55, 659 665.
237. Strauss, K.M., Martins, L.M., Plun-Favreau, H., Marx, F.P., Kautzmann, S., Berg, D., Gasser, T., Wszolek, Z., Muller, T., Bornemann, A., Wolburg, H., Downward, J., Riess, O., Schulz, J.B. Kruger, R 2005) Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease. Hum Mol Genet 14, 2099 2111.
238. Sun, M., Latourelle, J.C., Wooten, F., et al 2006) Influence of heterozygosity for Parkin mutation on onset age in familial Parkinson disease The GenePD study. Arch Neurol 63, 826 832.
239. Susin, S.A., Lorenzo, H.K., Zamzami, N., Marzo, I., Snow, B.E., Brothers, G.M., Mangion, J., Jacotot, E., Costantini, P., Loeffler, M., Larochette, N., Goodlett, D.R., Aebersold, R., Siderovski, D.P., Penninger, J.M. Kroemer, G 1999) Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397, 441 446.
240. Swerdlow, R.H., Parks, J.K., Miller, S.W., Tuttle, J.B., Trimmer, P.A., Sheehan, J.P., Bennett, J.P., Davis, R.E. Parker, W.D 1996) Origin and functional consequences of the complex I defect in Parkinson's disease. Ann Neurol 40, 663 671.
241. Tan, D.X., Manchester, L.C., Reiter, R.J., Qi, W.B., Karbownik, M. Calvo, J.R 2000a) Significance of melatonin in antioxidative defense system: reactions and products. Biol Signals Recept 9, 137 159.
242. Tan, E.K., Khajavi, M., Thornby, J.I., Nagamitsu, S., Jankovic, J. Ashizawa, T 2000b) Variability and validity of polymorphism association studies in Parkinson's disease. Neurology 55, 533 538.
243. Tan, E.K., Yew, K., Chua, E., Puvan, K., Shen, H., Lee, E., Puong, K.Y., Zhao, Y., Pavanni, R., Wong, M.C., Jamora, D., de Silva, D., Moe, K.T., Woon, F.P., Yuen, Y. Tan, L 2006) PINK1 mutations in sporadic early-onset Parkinson's disease. Mov Disord 21, 789 793.
244. Tanaka, Y., Engelender, S., Igarashi, S., Rao, R.K., Wanner, T., Tanzi, R.E., Sawa, A., Dawson, V.L., Dawson, T.M. Ross, C.A 2001) Inducible expression of mutant alpha-synuclein decreases proteasome activity and increases sensitivity to mitochondria-dependent apoptosis. Hum Mol Genet 10, 919 926.
245. Tatton, N.A 2000) Increased caspase 3 and Bax immunoreactivity accompany nuclear GAPDH translocation and neuronal apoptosis in Parkinson's disease. Exp Neurol 166, 29 43.
246. Tatton, W., Chalmers-Redman, R. Tatton, N 2003a) Neuroprotection by deprenyl and other propargylamines: glyceraldehyde-3-phosphate dehydrogenase rather than monoamine oxidase B. J Neural Transm 110, 509 515.
247. Tatton, W.G., Chalmers-Redman, R., Brown, D. Tatton, N 2003b) Apoptosis in Parkinson's disease: signals for neuronal degradation. Ann Neurol 53, S61 S70.
248. The NINDS NET-PD Investigators (2007) A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease. Neurology 68, 20 28.
249. Thomas, B. Mohanakumar, K.P 2004) Melatonin protects against oxidative stress caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the mouse nigrostriatum. J Pineal Res 36, 25 32.
250. Turrens, J.F 2003) Mitochondrial formation of reactive oxygen species. J Physiol Lond 552, 335 344.
251. Valente, E.M., Abou-Sleiman, P.M., Caputo, V., et al 2004) Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 304, 1158 1160.
252. Vatassery, G.T., Smith, W.E., Quach, H.T. Lai, J.C.K 1995) In-vitro oxidation of vitamin-e, vitamin-c, thiols and cholesterol in rat-brain mitochondria incubated with free-radicals. Neurochem Int 26, 527 535.
253. Verhagen, A.M., Silke, J., Ekert, P.G., Pakusch, M., Kaufmann, H., Connolly, L.M., Day, C.L., Tikoo, A., Burke, R., Wrobel, C., Moritz, R.L., Simpson, R.J. Vaux, D.L 2002) HtrA2 promotes cell death through its serine protease activity and its ability to antagonize inhibitor of apoptosis proteins. J Biol Chem 277, 445 454.
254. Wakamatsu, K., Fujikawa, K., Zucca, F.A., Zecca, L. Ito, S 2003) The structure of neuromelanin as studied by chemical degradative methods. J Neurochem 86, 1015 1023.
255. Waldmeier, P., Bozyczko-Coyne, D., Williams, M. Vaught, J.L 2006) Recent clinical failures in Parkinson's disease with apoptosis inhibitors underline the need for a paradigm shift in drug discovery for neurodegenerative diseases. Biochem Pharmacol 72, 1197 1206.
256. Wallimann, T., Wyss, M., Brdiczka, D., Nicolay, K. Eppenberger, H.M 1992) Intracellular compartmentation, structure and function of creatine-kinase isoenzymes in tissues with high and fluctuating energy demands - the phosphocreatine circuit for cellular-energy homeostasis. Biochem J 281, 21 40.
257. van der Walt, J.M., Nicodemus, K.K., Martin, E.R., et al 2003) Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease. Am J Hum Genet 72, 804 811.
258. Wang, C., Ko, H.S., Thomas, B., Tsang, F., Chew, K.C.M., Tay, S.P., Ho, M.W.L., Lim, T.M., Soong, T.W., Pletnikova, O., Troncoso, J., Dawson, V.L., Dawson, T.M. Lim, K.L 2005) Stress-induced alterations in parkin solubility promote parkin aggregation and compromise parkin's protective function. Hum Mol Genet 14, 3885 3897.
259. Wang, D.L., Qian, L., Xiong, H., Liu, J.D., Neckameyer, W.S., Oldham, S., Xia, K., Wang, J.Z., Bodmer, R. Zhang, Z.H 2006) Antioxidants protect PINK1-dependent dopaminergic neurons in Drosophila. Proc Natl Acad Sci U S A 103, 13520 13525.
260. Wang, J.Z., Wei, Q.Q., Wang, C.Y., Hill, W.D., Hess, D.C. Dong, Z 2004) Minocycline up-regulates Bcl-2 and protects against cell death in mitochondria. J Biol Chem 279, 19948 19954.
261. West, A., Periquet, M., Lincoln, S., Lucking, C.B., Nicholl, D., Bonifati, V., Rawal, N., Gasser, T., Lohmann, E., Deleuze, J.F., Maraganore, D., Levey, A., Wood, N., Durr, A., Hardy, J., Brice, A. Farrer, M 2002) Complex relationship between parkin mutations and Parkinson disease. Am J Med Genet 114, 584 591.
262. West, A.B., Moore, D.J., Biskup, S., Bugayenko, A., Smith, W.W., Ross, C.A., Dawson, V.L. Dawson, T.M 2005) Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci U S A 102, 16842 16847.
263. Whitworth, A.J., Wes, P.D. Pallanck, L.J 2006) Drosophila models pioneer a new approach to drug discovery for Parkinson's disease. Drug Discov Today 11, 119 126.
264. Wu, D.C., Jackson-Lewis, V., Vila, M., Tieu, K., Teismann, P., Vadseth, C., Choi, D.K., Ischiropoulos, H. Przedborski, S 2002) Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine mouse model of Parkinson disease. J Neurosci 22, 1763 1771.
265. Wu, R.M., Chen, R.C. Chiueh, C.C 2000) Effect of MAO-B inhibitors on MPP+ toxicity in vivo. Reactive Oxygen Species Radiat Mol Biol 899, 255 261.
266. Xie, Y.X., Bezard, E. Zhao, B.L 2005) Investigating the receptor-independent neuroprotective mechanisms of nicotine in mitochondria. J Biol Chem 280, 32405 32412.
267. Yang, L.C., Sugama, S., Chirichigno, J.W., Gregorio, J., Lorenzl, S., Shin, D.H., Browne, S.E., Shimizu, Y., Joh, T.H., Beal, M.F. Albers, D.S 2003) Minocycline enhances MPTP toxicity to dopaminergic neurons. J Neurosci Res 74, 278 285.
268. Yang, Y., Gehrke, S., Haque, M.E., Imai, Y., Kosek, J., Yang, L., Beal, M.F., Nishimura, I., Wakamatsu, K., Ito, S., Takahashi, R. Lu, B 2005) Inactivation of Drosophila DJ-1 leads to impairments of oxidative stress response and phosphatidylinositol 3-kinase/Akt signaling. Proc Natl Acad Sci U S A 102, 13670 13675.
269. Yang, Y.F., Gehrke, S., Imai, Y., Huang, Z.N., Ouyang, Y., Wang, J.W., Yang, L.C., Beal, M.F., Vogel, H. Lu, B.W 2006) Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused inactivation of Drosophila Pink1 is rescued by by Parkin. Proc Natl Acad Sci U S A 103, 10793 10798.
270. Yokota, T., Sugawara, K., Ito, K., Takahashi, R., Ariga, H. Mizusawa, H 2003) Down regulation of DJ-1 enhances cell death by oxidative stress, ER stress, and proteasome inhibition. Biochem Biophys Res Commun 312, 1342 1348.
271. Yong, V.W., Wells, J., Giuliani, F., Casha, S., Power, C. Metz, L.M 2004) The promise of minocycline in neurology. Lancet Neurol 3, 744 751.
272. Youdim, M.B., Ben Shachar, D. Riederer, P 1993) The possible role of iron in the etiopathology of Parkinson's disease. Mov Disord 8, 1 12.
273. Youdim, M.B., 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.
274. Youdim, M.B. Weinstock, M 2004) Therapeutic applications of selective and non-selective inhibitors of monoamine oxidase A and B that do not cause significant tyramine potentiation. Neurotoxicology 25, 243 250.
275. Youdim, M.B.H. Buccafusco, J.J 2005) Multi-functional drugs for various CNS targets in the treatment of neurodegenerative disorders. Trends Pharmacol Sci 26, 27 35.
276. Youdim, M.B.H., Fridkin, M. Zheng, H.L 2005) Bifunctional drug derivatives of MAO-B inhibitor rasagiline and iron chelator VK-28 as a more effective approach to treatment of brain ageing and ageing neurodegenerative diseases. Mech Ageing Dev 126, 317 326.
277. Youdim, M.B.H. Weinstock, M 2001) Molecular basis of neuroprotective activities of rasagiline and the anti-Alzheimer drug TV3326 [(N-propargyl-3R) aminoindan-5-YL)-ethyl methyl carbamate. Cell Mol Neurobiol 21, 555 573.
278. Zamzami, N. Kroemer, G 2001) The mitochondrion in apoptosis: how Pandora's box opens. Nat Rev Mol Cell Biol 2, 67 71.
279. Zarranz, J.J., Alegre, J., Gomez-Esteban, J.C., Lezcano, E., Ros, R., Ampuero, I., Vidal, L., Hoenicka, J., Rodriguez, O., Atares, B., Llorens, V., Gomez, T.E., Del Ser, T., Munoz, D.G. de Yebenes, J.G 2004) The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol 55, 164 173.
280. Zeevalk, G.D., Manzino, L., Sonsalla, P.K. Bernard, L.P 2007) Characterization of intracellular elevation of glutathione (GSH) with glutathione monoethyl ester and GSH in brain and neuronal cultures: relevance to Parkinson's disease. Exp Neurol 203, 512 520.
281. Zhang, L., Shimoji, M., Thomas, B., Moore, D.J., Yu, S.W., Marupudi, N.I., Torp, R., Torgner, I.A., Ottersen, O.P., Dawson, T.M. Dawson, V.L 2005a) Mitochondrial localization of the Parkinson's disease related protein DJ-1: implications for pathogenesis. Hum Mol Genet 14, 2063 2073.
282. Zhang, X., Xie, W., Qu, S., Pan, T., Wang, X. Le, W 2005b) Neuroprotection by iron chelator against proteasome inhibitor-induced nigral degeneration. Biochem Biophys Res Commun 333, 544 549.
283. Zheng, H., Gal, S., Weiner, L.M., Bar-Am, O., Warshawsky, A., Fridkin, M. Youdim, M.B.H 2005) Novel multifunctional neuroprotective iron chelator-monoamine oxidase inhibitor drugs for neurodegenerative diseases: in vitro studies on antioxidant activity, prevention of lipid peroxide formation and monoamine oxidase inhibition. J Neurochem 95, 68 78.
284. Zhou, H., Falkenburger, B.H., Schulz, J.B., Tieu, K., Xu, Z. Xia, X.G 2007) Silencing of the Pink1 gene expression by conditional RNAi does not induce dopaminergic neuron death in mice. Int J Biol Sci 3, 242 250.
285. Zhu, S., Stavrovskaya, I.G., Drozda, M., Kim, B.Y.S., Ona, V., Li, M.W., Sarang, S., Liu, A.S., Hartley, D.M., Du, C.W., Gullans, S., Ferrante, R.J., Przedborski, S., Kristal, B.S. Friedlander, R.M 2002) Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature 417, 74 78.
286. Zimprich, A., Biskup, S., Leitner, P., et al 2004) Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44, 601 607.