Role of Mitochondrial Dysfunction in Huntington’s Disease

Abstract

Abstract: Huntington’s disease (HD) is a fatal inherited neurodegenerative disorder with the progressive loss of striatal medium spiny neurons (MSN), caused by a polyglutamine expansion in the N-terminus of huntingtin protein. Pathogenic mechanism of HD is not fully understood, but increasing evidences indicate that dysfunction of mitochondria plays an important role in HD pathogenesis. The morphology and structure of mitochondria in HD are changed due to a series of pathogenic factors. Moreover, the activity and/or expression levels of some mitochondrial electron transport chain protein complexes are decreased, and the mitochondrial biogenesis is impaired by mutant huntingtin protein. Furthermore, dysregulation of mitochondrial Ca²⁺ homeostasis and excessive mitochondrial oxidant generation have been recently demonstrated in HD cells/neurons. All of these changes in HD mitochondria could cause the dysfunction of mitochondria, which in turn lead to cell death in HD cells, especially in neuron. This review will focus on the role of mitochondrial dysfunction in the pathogenesis of HD and the therapeutic strategy targeted on mitochondria for the treatment of HD.

Key words: Huntington&, rsquo, s disease, mitochondria, calcium signaling, reactive oxygen species

CLC Number:

R742， R964

WANG Jiu-Qiang, ZHU Shu, ZHU Xue-Fei, GUO Cai-Xia, TANG Tie-Shan. Role of Mitochondrial Dysfunction in Huntington’s Disease[J]. Acta Neuropharmacologica, 2012, 2(4): 47-57.

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