Mitochondria, oxidative damage, and inflammation in Parkinson's disease

Annals of the New York Academy of Sciences

Volumn 991, Issue , 2003, Pages 120-131

  Beal, M Flint ^a  

^a WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

Coenzyme Q10; Creatine; Inflammation; Microglia; Mitochondria; Oxidative damage

Indexed keywords

1,2,3,6 TETRAHYDRO 1 METHYL 4 PHENYLPYRIDINE; BIOCHEMICAL MARKER; FREE RADICAL; HYDROGEN PEROXIDE; HYDROXYL RADICAL; MANGANESE SUPEROXIDE DISMUTASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE); SUPEROXIDE DISMUTASE; UBIDECARENONE;

ANIMAL EXPERIMENT; ANIMAL MODEL; CONFERENCE PAPER; CONTROLLED STUDY; DNA DAMAGE; ENERGY METABOLISM; ENZYME DEFICIENCY; INFLAMMATION; MICROGLIA; MITOCHONDRIAL MEMBRANE; NERVE DEGENERATION; NONHUMAN; OXIDATIVE PHOSPHORYLATION; OXIDATIVE STRESS; PARKINSON DISEASE; PATHOGENESIS; RESPIRATORY CHAIN; SUBSTANTIA NIGRA;

ANIMALIA;

EID: 0038051345     PISSN: 00778923     EISSN: None     Source Type: Book Series    
DOI: 10.1111/j.1749-6632.2003.tb07470.x     Document Type: Conference Paper

References (115)

1. HALLIWELL, B. 1992. Reactive oxygen species and the central nervous system. J. Neurochem. 59: 1609-1623.
2. TURRENS, J.F., A. ALEXANDRE & A.L. LEHNINGER. 1985. Ubisemiquinone is the electron donor for superoxide formation by complex III of heart mitochondria. Arch. Biochem. Biophys. 237: 408-414.
3. BECKMAN, J.S. & J.P. CROW. 1993. Pathological implications of nitric oxide superoxide and peroxynitrite formation. Biochem. Soc. Trans. 21: 330-334.
4. ISCHIROPOULOS, H., L. ZHU, J. CHEN, et al. 1992. Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. Arch. Biochem. Biophys. 298: 431-437.
5. BEAL, M.F. 2001. Experimental models of Parkinson's disease. Nat. Rev. Neurosci. 2: 325-334.
6. SINGER, T.P., N. CASTAGNOLI, R.R. RAMSAY & A.J. TREVOR. 1987. Biochemical events in the development of parkinsonism induced by MPTP. J. Neurochem. 49: 1-8.
7. CLEETER, M.J.W., J.M. COOPER & A.H.V. SCHAPIRA. 1992. Irreversible inhibition of mitochondrial complex I by 1-methyl-4-phenylpyridium: evidence for free radical involvement. J. Neurochem. 58: 786-789.
8. + induces NADH dependent superoxide formation and enhances NADH dependent lipid peroxidation in bovine heart submitochondrial particles. Biochem. Biophys. Res. Commun. 170: 1049-1055.
9. SRIRAM, K., K.S. PAI, M.R. BOYD & V. RAVINDRANATH. 1997. Evidence for generation of oxidative stress in brain by MPTP: in vitro and in vivo studies in mice. Brain Res. 749: 44-52.
10. PRZEDBORSKI, S., V. KOSTIC, V. JACKSON-LEWIS, et al. 1992. Transgenic mice with increased Cu/Zn-superoxide dismutase activity are resistant to N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity. J. Neurosci. 12: 1658-1667.
11. ANDREASSEN, O.A., R.J. FERRANTE, A. DEDEOGLU, et al. 2001. Mice with a partial deficiency of manganese superoxide dismutase show increased vulnerability to the mitochondrial toxins malonate, 3- nitropropionic acid, and MPTP. Exp. Neurol. 167: 189-195.
12. KLIVENYI, P., O.A. ANDREASSEN, R.J. FERRANTE, et al. 2000. Inhibition of neuronal nitric oxide synthase protects against MPTP toxicity. Neuroreport 11: 1265-1268.
13. BINDOFF, L.A., M. BIRCH-MARTIN, N.E.F. CARTLIDGE, et al. 1989. Mitochondrial function in Parkinsons disease. Lancet 1: 49.
14. SCHAPIRA, A.H.V., J.M. COOPER, D. DEXTER, et al. 1990. Mitochondrial complex I deficiency in Parkinson's disease. J. Neurochem. 54: 823-827.
15. JANETZKY, B., S. HAUCK, M.B.H. YOUDIM, et al. 1994. Unaltered aconitase activity, but decreased complex I activity, in substantia nigra pars compacta of patients with Parkinson's disease. Neurosci. Lett. 169: 126-128.
16. MANN, V.M., J.M. COOPER, D. KRIGE, et al. 1992. Brain, skeletal muscle, and platelet homogenate mitochondrial function in Parkinson's disease. Brain 115: 333-342.
17. HATTORI, N., M. TANAKA, T. OZAWA & Y. MIZUNO. 1991. Immunohistochemical studies on complexes I, II, III and IV of mitochondria in Parkinson's disease. Ann. Neurol. 30: 563-571.
18. SWERDLOW, R.H., J.K. PARKS, S.W. MILLER, et al. 1996. Origin and functional consequences of the complex I defect in Parkinson's disease. Ann. Neurol. 40: 663-671.
19. GU, M., J.M. COOPER, J.W. TAANMAN & A.H.V. SCHAPIRA. 1998. Mitochondrial DNA transmission of the mitochondrial defect in Parkinson's disease. Ann. Neurol. 44: 177-186.
20. SHEEHAN, J.P., R.H. SWERDLOW, W.D. PARKER, et al. 1997. Altered calcium homeostasis in cells transformed by mitochondria from individuals with Parkinson's disease. J. Neurochem. 68: 1221-1233.
21. SIMON, D.K., R. MAYEUX, K. MARDER, et al. 2000. Mitochondrial DNA mutations in complex I and tRNA genes in Parkinson's disease. Neurology 54: 703-709.
22. DEXTER, D.T., C.J. CARTER, F.R. WELLS, et al. 1989. Basal lipid peroxidation in substantia nigra is increased in Parkinson's disease. J. Neurochem. 52: 381-389.
23. DEXTER, D.T., A.E. HOLLY, W.D. FLITTER, et al. 1994. Increased levels of lipid hydroperoxides in the Parkinsonian substantia nigra: an HPLC and ESR study. Mov. Disord. 9: 92-97.
24. ALAM, Z.I., S.E. DANIEL, A.J. LEES, et al. 1997. A generalised increase in protein carbonyls in the brain in Parkinson's but not incidental Lewy body disease. J. Neurochem. 69: 1326-1329.
25. ALAM, Z.I., A. JENNER, S.E. DANIEL, et al. 1997. Oxidative DNA damage in the Parkinsonian brain: an apparent selective increase in 8-hydroxyguanine levels in substantia nigra. J. Neurochem. 69: 1196-1203.
26. SANCHEZ-RAMOS, J.R., E. OVERVIK & B.N. AMES. 1994. A marker of oxyradical-mediated DNA damage (8-hydroxy-2′ deoxyguanosine) is increased in nigro-striatum of Parkinson's disease brain. Neurodegeneration. 3: 197-204.
27. SHERGILL, J.K., R. CAMMACK, C.E. COOPER, et al. 1996. Detection of nitrosyl complexes in human substantia nigra, in relation to Parkinson's disease. Biochem. Biophys. Res. Commun. 228: 298-305.
28. PERRY, T.L., D.V. GODIN & S. HANSEN. 1982. Parkinson's disease: a disorder due to nigral glutathione deficiency? Neurosci. Lett. 33: 305-310.
29. PERRY, T.L. & V.W. YONG. 1986. Idiopathic Parkinson's disease, progressive supranuclear palsy and glutathione metabolism in the substantia nigra of patients. Neurosci. Lett. 67: 269-274.
30. RIEDERER, P., J.-W. PARK & B. AMES. 1989. Transition metals, ferritin, glutathione, and ascorbic in parkinsonian brains. J. Neurochem. 52: 515-520.
31. SOFIC, E., K.W. LANGE, K. JELLINGER & P. RIEDERER. 1992. Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson's disease. Neurosci. Lett. 142: 128-130.
32. DEXTER, D.T., J. SIAN, S. ROSE, et al. 1994. Indices of oxidative stress and mitochondrial function in individuals with incidental Lewy body disease. Ann. Neurol. 35: 38-44.
33. MCGEER, P.L., S. ITAGAKI, B.E. BOYES & E.G. MCGEER. 1988. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains. Neurology 38: 1285-1291.
34. MIRZA, Z.N., M. KATO, H. KIMURA, et al. 2002. Fenoterol inhibits superoxide anion generation by human polymorphonuclear leukocytes via beta-adrenoceptor-dependent and -independent mechanisms. Ann. Allergy Asthma Immunol. 88: 494-500.
35. FLOYD, R.A. 1999. Antioxidants, oxidative stress, and degenerative neurological disorders. Proc. Soc. Exp. Biol. Med. 222: 236-245.
36. RAIVICH, G., L.L. JONES, A. WERNER, et al. 1999. Molecular signals for glial activation: pro- and anti-inflammatory cytokines in the injured brain. Acta Neurochir. Suppl. 73: 21-30.
37. KIM, W.G., R.P. MOHNEY, B. WILSON, et al. 2000. Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: role of microglia. J. Neurosci. 20: 6309-6316.
38. BABIOR, B.M. 1999. NADPH oxidase: an update. Blood 93: 1464-1476.
39. GOOD, P.F., A. HSU, P. WERNER, et al. 1998. Protein nitration in Parkinson's disease. J. Neuropathol. Exp. Neurol. 57: 338-339.
40. GIASSON, B.I., J.E. DUDA, I.V. MURRAY, et al. 2000. Oxidative damage linked to neuro-degeneration by selective alpha-synuclein nitration in synucleinopathy lesions. Science 290: 985-989.
41. MCGEER, P.L., K. YASOJIMA & E.G. MCGEER. 2001. Inflammation in Parkinson's disease. Adv. Neurol. 86: 83-89.
42. MOGI, M., M. HARADA, P. RIEDERER, et al. 1994. Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients. Neurosci. Lett. 165: 208-210.
43. BOKA, G., P. ANGLADE, D. WALLACH, et al. 1994. Immunocytochemical analysis of tumor necrosis factor and its receptors in Parkinson's disease. Neurosci. Lett. 172: 151-154.
44. HUNOT, S., N. DUGAS, B. FAUCHEUX, et al. 1999. FcepsilonRII/CD23 is expressed in Parkinson's disease and induces, in vitro, production of nitric oxide and tumor necrosis factor-alpha in glial cells. J. Neurosci. 19: 3440-3447.
45. MOGI, M., M. HARADA, T. KONDO, et al. 1994. Interleukin-1 beta, interleukin-6, epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients. Neurosci. Lett. 180: 147-150.
46. BLUM-DEGEN, D., T. MULLER, W. KUHN, et al. 1995. Interleukin-1 beta and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer's and de novo Parkinson's disease patients. Neurosci. Lett. 202: 17-20.
47. MULLER, T., D. BLUM-DEGEN, H. PRZUNTEK & W. KUHN. 1998. Interleukin-6 levels in cerebrospinal fluid inversely correlate to severity of Parkinson's disease. Acta Neurol Scand. 98: 142-144.
48. MCGEER, P.L., K. YASOJIMA & E.G. MCGEER. 2002. Association of interleukin-1beta polymorphisms with idiopathic Parkinson's disease. Neurosci. Lett. 326: 67-69.
49. SCHULTE, T., L. SCHOLS, T. MULLER, et al. 2002. Polymorphisms in the interleukin-1 alpha and beta genes and the risk for Parkinson's disease. Neurosci. Lett. 326: 70-72.
50. KOHUTNICKA, M., E. LEWANDOWSKA, I. KURKOWSKA-JASTRZEBSKA, et al. 1998. Microglial and astrocytic involvement in a murine model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Immunopharmacology 39: 167-180.
51. KURKOWSKA-JASTRZEBSKA, I., A. WRONSKA, M. KOHUTNICKA, et al. 1999. The inflammatory reaction following 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine intoxication in mouse. Exp. Neurol. 156: 50-61.
52. WU, H., S.B. KANATOUS, F.A. THURMOND, et al. 2002. Regulation of mitochondrial biogenesis in skeletal muscle by CaMK. Science. 296: 349-352.
53. MOGI, M., A. TOGARI, M. OGAWA, et al. 1998. Effects of repeated systemic administration of 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP) to mice on interleukin-1beta and nerve growth factor in the striatum. Neurosci. Lett. 250: 25-28.
54. KLIVENYI, P., R.J. FERRANTE, R.T. MATTHEWS, et al. 1999. Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis. Nature Med. 5: 347-350.
55. DU, Y., Z. MA, S. LIN, et al. 2001. Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson's disease. Proc. Natl. Acad. Sci. USA 98: 14669-14674.
56. ZHU, S., I.G. STAVROVSKAYA, M. DROZDA, et al. 2002. Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature 417: 74-78.
57. LANGSTON, J.W., L.S. FORNO, J. TETRUD, et al. 1999. Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure. Ann. Neurol. 46: 598-605.
58. BETARBET, R., T.B. SHERER, G. MACKENZIE, et al. 2000. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat. Neurosci. 3: 1301-1306.
59. GAO, H.M., J. JIANG, B. WILSON, et al. 2002. Microglial activation-mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: relevance to Parkinson's disease. J. Neurochem. 81: 1285-1297.
60. AKIYAMA, H. & P.L. MCGEER. 1989. Microglial response to 6-hydroxydopamine-induced substantia nigra lesions. Brain Res. 489: 247-253.
61. CICCHETTI, F., A.L. BROWNELL, K. WILLIAMS, et al. 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.
62. HE, Q-P., M.-L. SMITH, P.-A. LI & B.K. SIESJO. 1997. Necrosis of the substantia nigra, pars reticulate, in flurothyl-induced status epilepticus is ameliorated by the spin trap α phenyl-N-tert-butyl nitrone. Free Radic. Biol. Med. 22: 917-922.
63. GAO, H.M., J.S. HONG, W. ZHANG & B. LIU. 2002. Distinct role for microglia in roten-one-induced degeneration of dopaminergic neurons. J. Neurosci. 22: 782-790.
64. LIBERATORE, G.T., V. JACKSON-LEWIS, S. VUKOSAVIC, et al. 1999. Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease. Nature Med. 5: 1403-1409.
65. DEHMER, T., J. LINDENAU, S. HAID, et al. 2000. Deficiency of inducible nitric oxide synthase protects against MPTP toxicity in vivo. J. Neurochem. 74: 2213-2216.
66. CAO, X. & J. PHILLIS. 1994. α-Phenyl-tert-butyl nitrone reduced cortical infarct and edema in rats subjected to focal ischemia. Brain Res. 644: 267-272.
67. ADAMS, J., Y. COLLACO-MORAES & J. DE BELLEROCHE. 1996. Cyclooxygenase-2 induction in cerebral cortex: an intracellular response to synaptic excitation. J. Neurochem. 66: 6-13.
68. HO, L., H. OSAKA, P.S. AISEN & G.M. PASINETTI. 1998. Induction of cyclooxygenase (COX)-2 but not COX-1 gene expression in apoptotic cell death. J. Neuroimmunol. 89: 142-149.
69. PLANAS, A.M., M.A. SORIANO, C. JUSTICIN & E. RODRIGUEZ-FARRE. 1999. Induction of cyclooxygenase-2 in the rat brain after a mild episode of focal ischemia without tissue inflammation or neural cell damage. Neurosci. Lett. 275: 141-144.
70. TOCCO, G., J. FREIRE-MOAR, S.S. SCHREIBER, et al. 1997. Maturational regulation and regional induction of cyclooxygenase-2 in rat brain: implications for Alzheimer's disease. Exp. Neurol. 144: 339-349.
71. MIRJANY, M., L. HO & G.M. PASINETTI. 2002. Role of cyclooxygenase-2 in neuronal cell cycle activity and glutamate-mediated excitotoxicity. J. Pharmacol. Exp. Ther. 301: 494-500.
72. ARAKI, E., C. FORSTER, J.M. DUBINSKY, et al. 2001. Cyclooxygenase-2 inhibitor ns-398 protects neuronal cultures from lipopolysaccharide-induced neurotoxicity. Stroke 32: 2370-2375.
73. BEZZI, P., M. DOMERCQ, L. BRAMBILLA, et al. 2001. CXCR4-activated astrocyte glutamate release via TNFalpha: amplification by microglia triggers neurotoxicity. Nat. Neurosci. 4: 702-710.
74. HEWETT, S.J., T.F. ULIASZ, A.S. VIDWANS & J.A. HEWETT. 2000. Cyclooxygenase-2 contributes to N-methyl-D-aspartate-mediated neuronal cell death in primary cortical cell culture. J. Pharmacol. Exp. Ther. 293: 417-425.
75. IADECOLA, C., K. NIWA, S. NOGAWA, et al. 2001. Reduced susceptibility to ischemic brain injury and N-methyl-D- aspartate-mediated neurotoxicity in cyclooxygenase-2-deficient mice. Proc. Natl. Acad. Sci. USA. 98: 1294-1299.
76. TEISMANN, P. & B. FERGER. 2001. Inhibition of the cyclooxygenase isoenzymes COX-1 and COX-2 provide neuroprotection in the MPTP-mouse model of Parkinson's disease. Synapse 39: 167-174.
77. FENG, Z., T. WANG, D. LI, et al. 2002. Cyclooxygenase-2-deficient mice are resistant to 1-methyl-4-phenyll, 2, 3, 6-tetrahydropyridine-induced damage of dopaminergic neurons in the substantia nigra. Neurosci. Lett. 329: 354.
78. ENOMOTO, M. & S. NISHIGUCHI. 2002. SEN viruses and treatment response in chronic hepatitis C virus. Lancet 359: 1780-1781.
79. FUJITA, K., Y. KAWARADA, K. TERADA, et al. 2000. Quantitative detection of apoptotic thymocytes in low-dose X-irradiated mice by an anti-single-stranded DNA antibody. J. Radiat. Res. (Tokyo) 41: 139-149.
80. MOREIRA, A.L., L. TSENOVA-BERKOVA, J. WANG, et al. 1997. Effect of cytokine modulation by thalidomide on the granulomatous response in murine tuberculosis. Tuber. Lung Dis. 78: 47-55.
81. SRIRAM, K., J.M. MATHESON, S.A. BENKOVIC, et al. 2002. Mice deficient in TNF receptors are protected against dopaminergic neurotoxicity: implications for Parkinson's disease. FASEB J. 16: 1474-1476.
82. BOIREAU, A., F. BORDIER, P. DUBEDAT, et al. 1997. Thalidomide reduces MPTP-induced decrease in striatal dopamine levels in mice. Neurosci. Lett. 234: 123-126.
83. DINTER, H., J. TSE, M. HALKS-MILLER, et al. 2000. The type 1V phosphodiesterase specific inhibitor mesopram inhibits experimental autoimmune encephalomyelitis in rodents. J. Neuroimmunol. 108: 136-146.
84. MARTINEZ, I., C. PUERTA, C. REDONDO & A. GARCIA-MERINO. 1999. Type IV phosphodiesterase inhibition in experimental allergic encephalomyelitis of Lewis rats: sequential gene expression analysis of cytokines, adhesion molecules and the inducible nitric oxide synthase. J. Neurol. Sci. 164: 13-23.
85. DUTTA, P., D.E. RYAN & R. TABRIZCHI. 2001. The influence of phosphodiesterase inhibitor, rolipram, on hemodynamics in lipopolysaccharide-treated rats. Jpn. J. Pharmacol. 85: 241-249.
86. HULLEY, P., J. HARTIKKA, S. ABDEL'AL, et al. 1995. Inhibitors of type IV phosphodiesterases reduce the toxicity of MPTP in substantia nigra neurons in vivo. Eur. J. Neurosci. 7: 2431-2440.
87. LEMBERGER, T., O. BRAISSANT, C. JUGE-AUBRY, et al. 1996. PPAR tissue distribution and interactions with other hormone-signaling pathways. Ann. N.Y. Acad. Sci. 804: 231-251.
88. FUJISAWA, H., T. OGURA, A. HOKARI, et al. 1995. Inducible nitric oxide synthase in a human glioblastoma cell line. J. Neurochem. 64: 85-91.
89. JIANG, C., A.T. TING & B. SEED. 1998. PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391: 82-86.
90. RICOTE, M., A.C. LI, T.M. WILLSON, et al. 1998. The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 391: 79-82.
91. KITAMURA, Y., J. KAKIMURA, Y. MATSUOKA, et al. 1999. Activators of peroxisome proliferator-activated receptor-gamma (PPARgamma) inhibit inducible nitric oxide synthase expression but increase heine oxygenase-1 expression in rat glial cells. Neurosci. Lett. 262: 129-132.
92. MARX, N., F. MACH, A. SAUTY, et al. 2000. Peroxisome proliferator-activated receptor-gamma activators inhibit IFN-gamma-induced expression of the T cell-active CXC chemokines IP-10, Mig, and I-TAC in human endothelial cells. J. Immunol. 164: 6503-6508.
93. SHU, H., B. WONG, G. ZHOU, et al. 2000. Activation of PPARalpha or gamma reduces secretion of matrix metalloproteinase 9 but not interleukin 8 from human monocytic THP-1 cells. Biochem. Biophys. Res. Commun. 267: 345-349.
94. URYU, S., S. TOKUHIRO, T. MURASUGI & T. ODA. 2002. A novel compound, RS-1178, specifically inhibits neuronal cell death mediated by beta-amyloid-induced macrophage activation in vitro. Brain Res. 946: 298-306.
95. FEINSTEIN, D.L., E. GALEA, V. GAVRILYUK, et al. 2002. Peroxisome proliferator-activated receptor-gamma agonists prevent experimental autoimmune encephalomyelitis. Ann. Neurol. 51: 694-702.
96. BREIDERT, T., J. CALLEBERT, M.T. HENEKA, et al. 2002. Protective action of the peroxisome proliferator-activated receptor-gamma agonist pioglitazone in a mouse model of Parkinson's disease. J. Neurochem. 82: 615-624.
97. KIM, M.O., Q. SI, J.N. ZHOU, et al. 2002. Interferon-beta activates multiple signaling cascades in primary human microglia. J. Neurochem. 81: 1361-1371.
98. DALLNER, G. & P.J. SINDELAR. 2000. Regulation of ubiquinone metabolism. Free Radic. Biol. Med. 29: 285-294.
99. NOACK, H., U. KUBE & W. AUGUSTIN. 1994. Relations between tocopherol depletion and coenzyme Q during lipid peroxidation in rat liver mitochondria. Free Radic. Res. 20: 375-386.
100. LASS, A. & R.S. SOHAL. 1998. Electron transport-linked ubiquinone-dependent recycling of α-tocopherol inhibits autooxidation of mitochondrial membranes. Arch. Biochem. Biophys. 352: 229-236.
101. BEAL, M.F. 2002. Coenzyme Q10 as a possible treatment for neurodegenerative diseases. Free Radic. Res. 36: 455-460.
102. MATTHEWS, R.T., L. YANG, B.G. JENKINS, et al. 1998. Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington's disease. J. Neurosci. 18: 156-163.
103. 10 and nicotinamide block striatal lesions produced by the mitochondrial toxin malonate. Ann. Neurol. 36: 882-888.
104. MATTHEWS, R.T., L. YANG, S. BROWNE, et al. 1998. Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Proc. Natl. Acad. Sci. USA 95: 8892-8897.
105. BEAL, M.F., R.T. MATTHEWS, A. TIELEMAN & C.W. SHULTS. 1998. Coenzyme Q10 attenuates the 1-methyl-1,2,3-etrahydropyridine (MPTP) induced loss of striatal dopamine and dopaminergic axons in aged mice. Brain Res. 783: 109-114.
106. 10 is reduced in mitochondria from parkinsonian patients. Ann. Neurol. 42: 261-264.
107. SHULTS, J. & A.L. MORROW. 2002. Use of quasi-least squares to adjust for two levels of correlation. Biometrics 58: 521-530.
108. DUNANT, Y., F. LOCTIN, J. MARSAL, et al. 1988. Energy metabolism and quantal acetylcholine release: effects of botulinum toxin, 1-fluoro-2,4-dinitrobenzene, and diamide in the Torpedo electric organ. J. Neurochem. 50: 431-439.
109. HEMMER, W. & T. WALLIMANN. 1993. Functional aspects of creatine kinase in brain. Dev. Neurosci. 15: 249-260.
110. BREWER, G.J. & T.W WALLIMANN. 2000. Protective effect of the energy precursor creatine against toxicity of glutamate and β-amyloid in rat hippocampal neurons. J. Neurochem. 74: 1968-1978.
111. MATTHEWS, R.T., R.J. FERRANTE, P. KLIVENYI, et al. 1999. Creatine and cyclocreatine attenuate MPTP neurotoxicity. Exp. Neurol. 157: 142-149.
112. BRUSTOVETSKY, N., T. BRUSTOVETSKY & J.M. DUBINSKY. 2001. On the mechanisms of neuroprotection by creatine and phosphocreatine. J. Neurochem. 76: 425-434.
113. FERRANTE, R.J., O.A. ANDREASSEN, B.G. JENKINS, et al. 2000. Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease. J. Neurosci. 20: 4389-4397.
114. KLEVENYI, P., O. ANDREASSEN, R.J. FERRANTE, et al. 1999. Transgenic mice expressing a dominant negative mutant interleukin-1beta converting enzyme show resistance to MPTP neurotoxicity. Neuroreport 10: 635-638.
115. ANDREASSEN, O.A., A. DEDEOGLU, R.J. FERRANTE, et al. 2001. Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington's disease. Neurobiol. Dis. 8: 479-491.