突变型亨廷顿蛋白、异常的线粒体动力学、线粒体轴突运输缺陷以及亨廷顿病中的选择性突触退化。
Mutant huntingtin, abnormal mitochondrial dynamics, defective axonal transport of mitochondria, and selective synaptic degeneration in Huntington's disease.
作者信息
Reddy P Hemachandra, Shirendeb Ulziibat P
机构信息
Neurogenetics Laboratory, Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA.
出版信息
Biochim Biophys Acta. 2012 Feb;1822(2):101-10. doi: 10.1016/j.bbadis.2011.10.016. Epub 2011 Nov 4.
Abstract
Huntington's disease (HD) is a progressive, fatal neurodegenerative disease caused by expanded polyglutamine repeats in the HD gene. HD is characterized by chorea, seizures, involuntary movements, dystonia, cognitive decline, intellectual impairment and emotional disturbances. Research into mutant huntingtin (Htt) and mitochondria has found that mutant Htt interacts with the mitochondrial protein dynamin-related protein 1 (Drp1), enhances GTPase Drp1 enzymatic activity, and causes excessive mitochondrial fragmentation and abnormal distribution, leading to defective axonal transport of mitochondria and selective synaptic degeneration. This article summarizes latest developments in HD research and focuses on the role of abnormal mitochondrial dynamics and defective axonal transport in HD neurons. This article also discusses the therapeutic strategies that decrease mitochondrial fragmentation and neuronal damage in HD.
摘要
亨廷顿舞蹈症（HD）是一种由HD基因中多聚谷氨酰胺重复序列扩增引起的进行性、致命性神经退行性疾病。HD的特征包括舞蹈症、癫痫发作、不自主运动、肌张力障碍、认知能力下降、智力障碍和情绪障碍。对突变型亨廷顿蛋白（Htt）和线粒体的研究发现，突变型Htt与线粒体蛋白动力相关蛋白1（Drp1）相互作用，增强GTP酶Drp1的酶活性，并导致线粒体过度分裂和分布异常，从而导致线粒体轴突运输缺陷和选择性突触退化。本文总结了HD研究的最新进展，并重点关注线粒体动力学异常和轴突运输缺陷在HD神经元中的作用。本文还讨论了减少HD中线粒体分裂和神经元损伤的治疗策略。
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Mutant huntingtin's interaction with mitochondrial protein Drp1 impairs mitochondrial biogenesis and causes defective axonal transport and synaptic degeneration in Huntington's disease.突变型亨廷顿蛋白与线粒体蛋白 Drp1 的相互作用会损害线粒体生物发生，导致亨廷顿病中的轴突运输缺陷和突触退化。
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