부산대학교 도서관

Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder characterized by progressive motor dysfunction, emotional disturbances, dementia, and weight loss. It is caused by an expanded trinucleotide CAG repeat in the gene coding for the protein, huntingtin. Although no one specific interaction of mutant huntingtin has been suggested to be the pathologic trigger, a large body of evidence suggests that, in both the human condition and in HD mice, oxidative stress may play a role in the pathogenesis of HD. Increased levels of oxidative damage products, including protein nitration, lipid peroxidation, DNA oxidation, and exacerbated lipofuscin accumulation, occur in HD. Strong evidence exists for early oxidative stress in HD, coupled with mitochondrial dysfunction, each exacerbating the other and leading to an energy deficit. If oxidative damage plays a role in HD, then therapeutic strategies that reduce reactive oxygen species may ameliorate the neurodegenerative process. Two such strategies, using coenzyme Q10 and creatine, have been proposed. Although each agent has had limited efficacy in HD patients, the optimal therapeutic dose may have been underestimated. High-dose coenzyme Q10 and creatine are safe and tolerable in HD patients and are currently under investigation. In addition, there are parallels in reducing markers of oxidative stress in both HD mice and HD patients after treatment. It is likely that high-dose coenzyme Q10, creatine, or both agents, will represent a cornerstone defense in ameliorating the progression of HD. [ABSTRACT FROM AUTHOR]