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Bioenergetics in Huntington's Disease
Author(s) -
GRÜNEWALD THOMAS,
BEAL M. FLINT
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb07827.x
Subject(s) - neurodegeneration , excitotoxicity , huntington's disease , bioenergetics , oxidative stress , pathogenesis , disease , neuroscience , biology , huntingtin , programmed cell death , glutamate receptor , mechanism (biology) , microbiology and biotechnology , apoptosis , mitochondrion , genetics , medicine , pathology , immunology , endocrinology , receptor , philosophy , epistemology
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, huntingtin. The length of the resulting polyglutamine extensions correlates with lower age of onset and a higher density of ubiquitine‐positive neuronal intranuclear inclusions. Recently it has been proposed that mutant huntingtin 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 resporatory chain defects in pathogenesis of HD.