[The role of mitochondria in the pathogenesis of Huntington's disease].

Huntington's disease (HD) is an autosomal-dominant neurodegenerative hereditary disorder that gradually robs affected individuals of memory, cognitive skills and normal movements. It is originated by the mutation of the gene encoding the huntingtin-protein (Htt). Htt with an abnormal stretch of above 35 glutamines in the N terminus (mHtt) results in HD. The observed symptoms result from the selective loss of neurons within the central nervous system, mainly in the striatum but also in the cortex. At present increasing numbers of data indicate that mitochondrial functioning is affected by mHtt and the resulting mitochondrial impairments may occur early enough to contribute to mHtt-induced toxicity and the HD pathogenic mechanism. Here, we review how mHtt might cause mitochondrial dysfunction by either perturbing transcription of nuclear-encoded mitochondrial proteins or by direct interaction with mitochondrial proteins. In addition, we discuss therapeutic opportunities for HD based on protection against mitochondrial dysfunction.