Evidence of oxidant damage in Huntington's disease: Translational strategies using antioxidants

Annals of the New York Academy of Sciences

Volumn 1147, Issue , 2008, Pages 79-92

  Stack, Edward C ^a   Matson, Wayne R ^a   Ferrante, Robert J ^a,b  

^a BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Coenzyme Q10; Creatine; Oxidative stress

Indexed keywords

ANTIOXIDANT; BIOLOGICAL MARKER; CREATINE; HUNTINGTIN; LIPOFUSCIN; REACTIVE OXYGEN METABOLITE; TRINUCLEOTIDE; UBIDECARENONE;

AUTOSOMAL DOMINANT INHERITANCE; CONFERENCE PAPER; DEGENERATIVE DISEASE; DISEASE COURSE; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DRUG MEGADOSE; GENETIC CODE; HUMAN; HUNTINGTON CHOREA; LIPID PEROXIDATION; NITRATION; OXIDATION; OXIDATIVE STRESS; PATHOGENESIS; PROTEIN PROTEIN INTERACTION; TRINUCLEOTIDE REPEAT; WEIGHT REDUCTION;

MUS;

EID: 57649171133     PISSN: 00778923     EISSN: 17496632     Source Type: Book Series    
DOI: 10.1196/annals.1427.008     Document Type: Conference Paper

References (122)

1. Huntington's Disease Collaborative Research Group. 1993. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72 : 971 983.
2. Davies, S. & D.B. Ramsden. 2001. Huntington's disease. Mol. Pathol. 54 : 409 413.
3. Koroshetz, W.J., R.H. Myers & J.B. Martin. 1992. The neurology of Huntington's disease. In Movement Disorders in Neurology and Neuropsychiatry. A. Joseph & R. Young, Eds. : 173 190. Blackwell Scientific Publications. Boston, MA.
4. Kremer, B. 2002. Clinical neurology of Huntington's disease. In Huntington's Disease. G. Bates, P. Harper & L. Jones, Eds. : 28 61. Oxford University Press. Oxford, United Kingdom.
5. Myers, R.H., J.P. Vonsattel, T.J. Stevens, et al. 1988. Clinical and neuropathologic assessment of severity in Huntington's disease. Neurology 38 : 341 347.
6. Huntington, G. 1872. On chorea. Med. Surg. Reporter 26 : 317 321.
7. Jelgersma, G. 1908. Neue anatomische Befunde bei Paralysis agitans und bei chronischer Chorea. Neurologisches Zentralblatt 27 : 995 996.
8. Vonsattel, J.P., R.H. Myers, T.J. Stevens, et al. 1985. Neuropathological classification of Huntington's disease. J. Neuropathol. Exp. Neurol. 44 : 559 577.
9. Kowall, N.W., R.J. Ferrante, M.F. Beal, et al. 1987. Neuropeptide Y, somatostatin, and reduced nicotinamide adenine dinucleotide phosphate diaphorase in the human striatum: A combined immunocytochemical and enzyme histochemical study. Neuroscience 20 : 817 828.
10. Albin, R.L., A. Reiner, K.D. Anderson, et al. 1990. Striatal and nigral neuron subpopulations in rigid Huntington's disease: Implications for the functional anatomy of chorea and rigidity-akinesia. Ann. Neurol. 27 : 357 365.
11. Ferrante, R.J., M.F. Beal, N.W. Kowall, et al. 1987. Sparing of acetylcholinesterase-containing striatal neurons in Huntington's disease. Brain Res. 411 : 162 166.
12. Ferrante, R.J. & N.W. Kowall. 1987. Tyrosine hydroxylase-like immunoreactivity is distributed in the matrix compartment of normal human and Huntington's disease striatum. Brain Res. 416 : 141 146.
13. Ferrante, R.J., N.W. Kowall, M.F. Beal, et al. 1987. Morphologic and histochemical characteristics of a spared subset of striatal neurons in Huntington's disease. J. Neuropathol. Exp. Neurol. 46 : 12 27.
14. Ferrante, R.J., N.W. Kowall, M.F. Beal, et al. 1985. Selective sparing of a class of striatal neurons in Huntington's disease. Science 230 : 561 563.
15. Ferrante, R.J., N.W. Kowall & E.P. Richardson, Jr. 1991. Proliferative and degenerative changes in striatal spiny neurons in Huntington's disease: A combined study using the section-Golgi method and calbindin D28k immunocytochemistry. J. Neurosci. 11 : 3877 3887.
16. Ferrante, R.J., N.W. Kowall, E.P. Richardson, Jr. et al. 1986. Topography of enkephalin, substance P and acetylcholinesterase staining in Huntington's disease striatum. Neurosci. Lett. 71 : 283 288.
17. Goto, S., A. Hirano & R.R. Rojas-Corona. 1989. An immunohistochemical investigation of the human neostriatum in Huntington's disease. Ann. Neurol. 25 : 298 304.
18. Seto-Ohshima, A., P.C. Emson, E. Lawson, et al. 1988. Loss of matrix calcium-binding protein-containing neurons in Huntington's disease. Lancet 1 : 1252 1255.
19. Szebenyi, G., G.A. Morfini, A. Babcock, et al. 2003. Neuropathogenic forms of huntingtin and androgen receptor inhibit fast axonal transport. Neuron 40 : 41 52.
20. Trushina, E., R.B. Dyer, J.D. Badger, 2nd. et al. 2004. Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitro. Mol. Cell Biol. 24 : 8195 8209.
21. Gauthier, L.R., B.C. Charrin, M. Borrell-Pages, et al. 2004. Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell 118 : 127 138.
22. Difiglia, M., E. Sapp, K. Chase, et al. 1995. Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons. Neuron 14 : 1075 1081.
23. Difiglia, M., E. Sapp, K.O. Chase, et al. 1997. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277 : 1990 1993.
24. Kuemmerle, S., C.A. Gutekunst, A.M. Klein, et al. 1999. Huntington aggregates may not predict neuronal death in Huntington's disease. Ann. Neurol. 46 : 842 849.
25. Ferrante, R.J., C.A. Gutekunst, F. Persichetti, et al. 1997. Heterogeneous topographic and cellular distribution of huntingtin expression in the normal human neostriatum. J. Neurosci. 17 : 3052 3063.
26. Beal, M.F. & R.J. Ferrante. 2004. Experimental therapeutics in transgenic mouse models of Huntington's disease. Nat. Rev. Neurosci. 5 : 373 384.
27. Beal, M.F. 1998. Mitochondrial dysfunction in neurodegenerative diseases. Biochim. Biophys. Acta 1366 : 211 223.
28. Beal, M.F. 1999. Mitochondria, NO and neurodegeneration. Biochem. Soc. Symp. 66 : 43 54.
29. Calabrese, V., E. Guagliano, M. Sapienza, et al. 2006. Redox regulation of cellular stress response in neurodegenerative disorders. Ital. J. Biochem. 55 : 263 282.
30. Mancuso, C., G. Scapagini, D. Curro, et al. 2007. Mitochondrial dysfunction, free radical generation and cellular stress response in neurodegenerative disorders. Front Biosci. 12 : 1107 1123.
31. Beal, M.F. 1992. Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses? Ann. Neurol. 31 : 119 130.
32. Browne, S.E., A.C. Bowling, U. Macgarvey, et al. 1997. Oxidative damage and metabolic dysfunction in Huntington's disease: Selective vulnerability of the basal ganglia. Ann. Neurol. 41 : 646 653.
33. Ferrante, R.J., M.F. Beal & N.W. Kowall. 1994. Mechanisms of neuronal degeneration in Huntington's disease. In The Basal Ganglia IV: New Ideas and Data on Structure and Function. G. Percheron, Js. Mckenzie & J. Feger, Eds. : 149 161. Plenum Press. New York, NY.
34. Grunewald, T. & M.F. Beal. 1999. Bioenergetics in Huntington's disease. Ann. N. Y. Acad. Sci. 893 : 203 213.
35. Ross, C.A. & M.A. Poirier. 2004. Protein aggregation and neurodegenerative disease. Nat. Med. 10 Suppl : S10 S17.
36. Terman, A. & U.T. Brunk. 1998. Lipofuscin: Mechanisms of formation and increase with age. Apmis 106 : 265 276.
37. Sohal, R.S. & U.T. Brunk. 1989. Lipofuscin as an indicator of oxidative stress and aging. Adv. Exp. Med. Biol. 266 : 17 26.
38. Braak, H. & E. Braak. 1992. Allocortical involvement in Huntington's disease. Neuropathol. Appl. Neurobiol. 18 : 539 547.
39. Browne, S.E., R.J. Ferrante & M.F. Beal. 1999. Oxidative stress in Huntington's disease. Brain Pathol. 9 : 147 163.
40. Tellez-Nagel, I., A.B. Johnson & R.D. Terry. 1974. Studies on brain biopsies of patients with Huntington's chorea. J. Neuropathol. Exp. Neurol. 33 : 308 332.
41. Driggers, W.J., Holmquist, G.P., Ledoux, S.P. & Wilson, G.L. 1997. Mapping frequencies of endogenous oxidative damage and the kinetic response to oxidative stress in a region of rat mtDNA. Nucleic Acids Res. 25 : 4362 4369.
42. Butterworth, N.J., L. Williams, J.Y. Bullock, et al. 1998. Trinucleotide (CAG) repeat length is positively correlated with the degree of DNA fragmentation in Huntington's disease striatum. Neuroscience 87 : 49 53.
43. Dragunow, M., R.L. Faull, P. Lawlor, et al. 1995. In situ evidence for DNA fragmentation in Huntington's disease striatum and Alzheimer's disease temporal lobes. Neuroreport 6 : 1053 1057.
44. Portera-Cailliau, C., J.C. Hedreen, D.L. Price & V.E. Koliatsos. 1995. Evidence for apoptotic cell death in Huntington disease and excitotoxic animal models. J. Neurosci. 15 : 3775 3787.
45. Polidori, M.C., P. Mecocci, S.E. Browne, et al. 1999. Oxidative damage to mitochondrial DNA in Huntington's disease parietal cortex. Neurosci. Lett. 272 : 53 56.
46. Hersch, S.M., S. Gevorkian, K. Marder, et al. 2006. Creatine in Huntington disease is safe, tolerable, bioavailable in brain and reduces serum 8OH2'dG. Neurology 66 : 250 252.
47. Ferrante, R.J., S.E. Browne, L.A. Shinobu, et al. 1997. Evidence of increased oxidative damage in both sporadic and familial amyotrophic lateral sclerosis. J. Neurochem. 69 : 2064 2074.
48. Mecocci, P., U. Macgarvey, A.E. Kaufman, et al. 1993. Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain. Ann. Neurol. 34 : 609 616.
49. Alam, Z.I., B. Halliwell & P. Jenner. 2000. No evidence for increased oxidative damage to lipids, proteins, or DNA in Huntington's disease. J. Neurochem. 75 : 840 846.
50. Ferrante, R.J., N.W. Kowall, S.M. Hersch, et al. 1996. Immunohistochemical localization of markers of oxidative injury in Huntington's disease. 26th Annual Meeting of the Society for Neuroscience. Washington, DC.
51. Stoy, N., G.M. Mackay, C.M. Forrest, et al. 2005. Tryptophan metabolism and oxidative stress in patients with Huntington's disease. J. Neurochem. 93 : 611 623.
52. Beal, M.F., E. Brouillet, B.G. Jenkins, et al. 1993. Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. J. Neurosci. 13 : 4181 4192.
53. Brouillet, E., B.G. Jenkins, B.T. Hyman, et al. 1993. Age-dependent vulnerability of the striatum to the mitochondrial toxin 3-nitropropionic acid. J. Neurochem. 60 : 356 359.
54. Henshaw, R., B.G. Jenkins, J.B. Schulz, et al. 1994. Malonate produces striatal lesions by indirect NMDA receptor activation. Brain Res. 647 : 161 166.
55. Schulz, J.B., D.R. Henshaw, U. Macgarvey & M.F. Beal. 1996. Involvement of oxidative stress in 3-nitropropionic acid neurotoxicity. Neurochem. Int. 29 : 167 171.
56. Mangiarini, L., K. Sathasivam, M. Seller, et al. 1996. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87 : 493 506.
57. Stack, E.C., J.K. Kubilus, K. Smith, et al. 2005. Chronology of behavioral symptoms and neuropathological sequela in R6/2 Huntington's disease transgenic mice. J. Comp. Neurol. 490 : 354 370.
58. Bogdanov, M.B., O.A. Andreassen, A. Dedeoglu, et al. 2001. Increased oxidative damage to DNA in a transgenic mouse model of Huntington's disease. J. Neurochem. 79 : 1246 1249.
59. Browne, S.E. & M.F. Beal. 2006. Oxidative damage in Huntington's disease pathogenesis. Antioxid. Redox. Signal. 8 : 2061 2073.
60. Tabrizi, S.J., J. Workman, P.E. Hart, et al. 2000. Mitochondrial dysfunction and free radical damage in the Huntington R6/2 transgenic mouse. Ann. Neurol. 47 : 80 86.
61. Perez-Severiano, F., C. Rios & J. Segovia. 2000. Striatal oxidative damage parallels the expression of a neurological phenotype in mice transgenic for the mutation of Huntington's disease. Brain Res. 862 : 234 237.
62. Menalled, L.B., J.D. Sison, I. Dragatsis, et al. 2003. Time course of early motor and neuropathological anomalies in a knock-in mouse model of Huntington's disease with 140 CAG repeats. J. Comp. Neurol. 465 : 11 26.
63. Cui, L., H. Jeong, F. Borovecki, et al. 2006. Transcriptional repression of PGC-1 alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell 127 : 59 69.
64. Kuhl, D.E., M.E. Phelps, C.H. Markham, et al. 1982. Cerebral metabolism and atrophy in Huntington's disease determined by 18FDG and computed tomographic scan. Ann. Neurol. 12 : 425 434.
65. Gu, M., M.T. Gash, V.M. Mann, et al. 1996. Mitochondrial defect in Huntington's disease caudate nucleus. Ann. Neurol. 39 : 385 389.
66. Tabrizi, S.J., M.W. Cleeter, J. Xuereb, et al. 1999. Biochemical abnormalities and excitotoxicity in Huntington's disease brain. Ann. Neurol. 45 : 25 32.
67. Jenkins, B.G., H.D. Rosas, Y.C. Chen, et al. 1998. 1H NMR spectroscopy studies of Huntington's disease: Correlations with CAG repeat numbers. Neurology 50 : 1357 1365.
68. Koroshetz, W.J., B.G. Jenkins, B.R. Rosen & M.F. Beal. 1997. Energy metabolism defects in Huntington's disease and effects of coenzyme Q10. Ann. Neurol. 41 : 160 165.
69. Panov, A.V., J.R. Burke, W.J. Strittmatter & J.T. Greenamyre. 2003. In vitro effects of polyglutamine tracts on Ca2+-dependent depolarization of rat and human mitochondria: Relevance to Huntington's disease. Arch. Biochem. Biophys. 410 : 1 6.
70. Panov, A.V., C.A. Gutekunst, B.R. Leavitt, et al. 2002. Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines. Nat. Neurosci. 5 : 731 736.
71. Reiter, R.J., J. Cabrera, R.M. Sainz, et al. 1999. Melatonin as a pharmacological agent against neuronal loss in experimental models of Huntington's disease, Alzheimer's disease and parkinsonism. Ann. N. Y. Acad. Sci. 890 : 471 485.
72. Uz, T., P. Giusti, D. Franceschini, et al. 1996. Protective effect of melatonin against hippocampal DNA damage induced by intraperitoneal administration of kainate to rats. Neuroscience 73 : 631 636.
73. Tunez, I., P. Montilla, M. Del Carmen Munoz, et al. 2004. Protective effect of melatonin on 3-nitropropionic acid-induced oxidative stress in synaptosomes in an animal model of Huntington's disease. J. Pineal. Res. 37 : 252 256.
74. O'kane, D.J. & I.C. Gunsalus. 1948. Pyruvic acid metabolism: A factor required for oxidation by streptococcus faecalis. J. Bacteriol. 56 : 499 506.
75. Henriksen, E.J. 2006. Exercise training and the antioxidant alpha-lipoic acid in the treatment of insulin resistance and type 2 diabetes. Free Radic. Biol. Med. 40 : 3 12.
76. Packer, L., H.J. Tritschler & K. Wessel. 1997. Neuroprotection by the metabolic antioxidant alpha-lipoic acid. Free Radic. Biol. Med. 22 : 359 378.
77. Andreassen, O.A., R.J. Ferrante, A. Dedeoglu & M.F. Beal. 2001. Lipoic acid improves survival in transgenic mouse models of Huntington's disease. Neuroreport 12 : 3371 3373.
78. Halliwell, B. & J.M. Gutteridge. 1984. Lipid peroxidation, oxygen radicals, cell damage, and antioxidant therapy. Lancet 1 : 1396 1397.
79. Santamaria, A., R. Salvatierra-Sanchez, B. Vazquez-Roman, et al. 2003. Protective effects of the antioxidant selenium on quinolinic acid-induced neurotoxicity in rats: In vitro and in vivo studies. J. Neurochem. 86 : 479 488.
80. Giandomenico, A.R., G.E. Cerniglia, J.E. Biaglow, et al. 1997. The importance of sodium pyruvate in assessing damage produced by hydrogen peroxide. Free Radic. Biol. Med. 23 : 426 434.
81. Chabrier, P., V. Roubert, J. Harnett, et al. 2001. New neuroprotective agents are potent inhibitors of mitochondrial toxins: In vivo and in vitro studies. 27th Annual Meeting of the Society for Neuroscience. New Orleans, LA.
82. Ryu, J.K., S.U. Kim & J.G. Mclarnon. 2003. Neuroprotective effects of pyruvate in the quinolinic acid rat model of Huntington's disease. Exp. Neurol. 183 : 700 704.
83. Andreassen, O.A., R.J. Ferrante, H.M. Huang, et al. 2001. Dichloroacetate exerts therapeutic effects in transgenic mouse models of Huntington's disease. Ann. Neurol. 50 : 112 117.
84. Klivenyi, P., R.J. Ferrante, G. Gardian, et al. 2003. Increased survival and neuroprotective effects of BN82451 in a transgenic mouse model of Huntington's disease. J. Neurochem. 86 : 267 272.
85. Crow, J.P., N.Y. Calingasan, J. Chen, et al. 2005. Manganese porphyrin given at symptom onset markedly extends survival of ALS mice. Ann. Neurol. 58 : 258 265.
86. Petri, S., M. Kiaei, K. Kipiani, et al. 2006. Additive neuroprotective effects of a histone deacetylase inhibitor and a catalytic antioxidant in a transgenic mouse model of amyotrophic lateral sclerosis. Neurobiol. Dis. 22 : 40 49.
87. Petersen, A., R.F. Castilho, O. Hansson, et al. 2000. Oxidative stress, mitochondrial permeability transition and activation of caspases in calcium ionophore A23187-induced death of cultured striatal neurons. Brain Res. 857 : 20 29.
88. Majewska, M.D. & J.A. Bell. 1990. Ascorbic acid protects neurons from injury induced by glutamate and NMDA. Neuroreport 1 : 194 196.
89. Miyamoto, M., T.H. Murphy, R.L. Schnaar & J.T. Coyle. 1989. Antioxidants protect against glutamate-induced cytotoxicity in a neuronal cell line. J. Pharmacol. Exp. Ther. 250 : 1132 1140.
90. Peyser, C.E., M. Folstein, G.A. Chase, et al. 1995. Trial of d-alpha-tocopherol in Huntington's disease. Am. J. Psychiatry 152 : 1771 1775.
91. Miyamoto, M. & J.T. Coyle. 1990. Idebenone attenuates neuronal degeneration induced by intrastriatal injection of excitotoxins. Exp. Neurol. 108 : 38 45.
92. Ranen, N.G., C.E. Peyser, J.T. Coyle, et al. 1996. A controlled trial of idebenone in Huntington's disease. Mov. Disord. 11 : 549 554.
93. Ryu, H., H.D. Rosas, S.M. Hersch & R.J. Ferrante. 2005. The therapeutic role of creatine in Huntington's disease. Pharmacol. Ther. 108 : 193 207.
94. Lawler, J.M., W.S. Barnes, G. Wu, et al. 2002. Direct antioxidant properties of creatine. Biochem. Biophys. Res. Commun. 290 : 47 52.
95. O'gorman, E., G. Beutner, M. Dolder, et al. 1997. The role of creatine kinase in inhibition of mitochondrial permeability transition. FEBS Lett. 414 : 253 257.
96. Bessman, S.P. & P.J. Geiger. 1981. Transport of energy in muscle: The phosphorylcreatine shuttle. Science 211 : 448 452.
97. Andreassen, O.A., A. Dedeoglu, R.J. Ferrante, et al. 2001. Creatine increases survival and delays motor symptoms in a transgenic animal model of Huntington's disease. Neurobiol. Dis. 8 : 479 491.
98. Carter, A.J., R.E. Muller, U. Pschorn & W. Stransky. 1995. Preincubation with creatine enhances levels of creatine phosphate and prevents anoxic damage in rat hippocampal slices. J. Neurochem. 64 : 2691 2699.
99. Dedeoglu, A., J.K. Kubilus, L. Yang, et al. 2003. Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington's disease transgenic mice. J. Neurochem. 85 : 1359 1367.
100. 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.
101. Klivenyi, P., R.J. Ferrante, R.T. Matthews, et al. 1999. Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis. Nat. Med. 5 : 347 350.
102. Matthews, R.T., R.J. Ferrante, P. Klivenyi, et al. 1999. Creatine and cyclocreatine attenuate MPTP neurotoxicity. Exp. Neurol. 157 : 142 149.
103. 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.
104. Zhu, S., M. Li, B.E. Figueroa, et al. 2004. Prophylactic creatine administration mediates neuroprotection in cerebral ischemia in mice. J. Neurosci. 24 : 5909 5912.
105. Shear, D.A., K.L. Haik & G.L. Dunbar. 2000. Creatine reduces 3-nitropropionic-acid-induced cognitive and motor abnormalities in rats. Neuroreport 11 : 1833 1837.
106. Kieburtz, K. 2001. Placebo-controlled trial of creatine in Huntington's disease. Huntington Study Group. Neurol. 56 : A386.
107. Verbessem, P., J. Lemiere, B.O. Eijnde, et al. 2003. Creatine supplementation in Huntington's disease: A placebo-controlled pilot trial. Neurology 61 : 925 930.
108. Tabrizi, S.J., A.M. Blamire, D.N. Manners, et al. 2003. Creatine therapy for Huntington's disease: Clinical and MRS findings in a 1-year pilot study. Neurology 61 : 141 142.
109. Foran, E.F., S.J. Del Signore, A. Markey, et al. 2006. Dose ranging and efficacy study of high-dose creatine in Huntington disease mouse models. 36th Annual Meeting of the Society for Neuroscience. Atlanta, GA.
110. Beal, M.F., D.R. Henshaw, B.G. Jenkins, et al. 1994. Coenzyme Q10 and nicotinamide block striatal lesions produced by the mitochondrial toxin malonate. Ann. Neurol. 36 : 882 888.
111. Ferrante, R.J., O.A. Andreassen, A. Dedeoglu, et al. 2002. Therapeutic effects of coenzyme Q10 and remacemide in transgenic mouse models of Huntington's disease. J. Neurosci. 22 : 1592 1599.
112. Lass, A., M.J. Forster & R.S. Sohal. 1999. Effects of coenzyme Q10 and alpha-tocopherol administration on their tissue levels in the mouse: Elevation of mitochondrial alpha-tocopherol by coenzyme Q10. Free Radic. Biol. Med. 26 : 1375 1382.
113. Schilling, G., M.L. Coonfield, C.A. Ross & D.R. Borchelt. 2001. Coenzyme Q10 and remacemide hydrochloride ameliorate motor deficits in a Huntington's disease transgenic mouse model. Neurosci. Lett. 315 : 149 153.
114. Stack, E.C., K.M. Smith, H. Ryu, et al. 2006. Combination therapy using minocycline and coenzyme Q10 in R6/2 transgenic Huntington's disease mice. Biochim. Biophys. Acta 1762 : 373 380.
115. Chan, T.S., J.X. Wilson & P.J. O'brien. 2004. Coenzyme Q cytoprotective mechanisms. Methods Enzymol. 382 : 89 104.
116. 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.
117. Feigin, A., K. Kieburtz, P. Como, et al. 1996. Assessment of coenzyme Q10 tolerability in Huntington's disease. Mov. Disord. 11 : 321 323.
118. Huntington Study Group. 2001. A randomized, placebo-controlled trial of coenzyme Q10 and remacemide in Huntington's disease. Neurology 57 : 397 404.
119. Shults, C.W., D. Oakes, K. Kieburtz, et al. 2002. Effects of coenzyme Q10 in early Parkinson's disease: Evidence of slowing of the functional decline. Arch. Neurol. 59 : 1541 1550.
120. Ferrante, K.L., J. Shefner, H. Zhang, et al. 2005. Tolerance of high-dose (3,000 mg/day) coenzyme Q10 in ALS. Neurology 65 : 1834 1836.
121. Shults, C.W., M.F. Beal, D. Song & D. Fontaine. 2004. Pilot trial of high dosages of coenzyme Q10 in patients with Parkinson's disease. Exp. Neurol. 188 : 491 494.
122. Smith, K.M., S. Matson, W.R. Matson, et al. 2006. Dose ranging and efficacy study of high-dose coenzyme Q10 formulations in Huntington's disease mice. Biochim. Biophys. Acta 1762 : 616 626.