Acta Neuropharmacologica››2012,Vol. 2››Issue (4): 47-57.

Previous ArticlesNext Articles

Role of Mitochondrial Dysfunction in Huntington’s Disease

WANG Jiu-Qiang1, ZHU Shu1, ZHU Xue-Fei1, GUO Cai-Xia2, TANG Tie-Shan1

  1. 1. State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China
    2. Laboratory of Disease Genomics and Individual Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China
  • Online:2012-08-26Published:2014-06-27
  • Contact:唐铁山,guocx@big.ac.cn, tangtsh@ioz.ac.cn
  • Supported by:

    科技部重大科学计划(No.2011CB965003、No.2011CB944302、No.2012CB944702),国家自然科学基金 (No.30970588、No.31170730、No.81371415) 和中科院百人计划项目的支持

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:

Baidu
map