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Journal Article
Review
Bioenergetics in Huntington's disease.
Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder with relentless course and prototypical clinical symptoms. In 1993 HD was associated with an expanded CAG triplet repeat stretch on chromosome 4 in the coding region of its target protein, huntington. The length of the resulting polyglutamine++ extensions correlates with lower age of onset and a higher density of ubiquitin-positive neuronal intranuclear inclusions. Recently it has been proposed that mutant huntington induces progressive neuronal cell death by an apoptotic mechanism. There is strong evidence that disturbances in cellular energy homeostasis and oxidative damage contribute to neurodegeneration. This review will summarize and discuss the current concepts that point towards an involvement of free radical-induced oxidative stress, glutamate excitotoxicity and mitochondrial respiratory chain defects in pathogenesis of HD.
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