亨廷顿病。
Huntington's Disease.
机构信息
Gladstone Institute of Neurological Disease, Taube-Koret Center for Huntington's Disease Research, Departments of Neurology and Physiology, University of California, San Francisco, 94158, USA.
出版信息
Cold Spring Harb Perspect Biol. 2011 Jun 1;3(6):a007476. doi: 10.1101/cshperspect.a007476.
Abstract
Huntington's disease (HD) is the most common inherited neurodegenerative disease and is characterized by uncontrolled excessive motor movements and cognitive and emotional deficits. The mutation responsible for HD leads to an abnormally long polyglutamine (polyQ) expansion in the huntingtin (Htt) protein, which confers one or more toxic functions to mutant Htt leading to neurodegeneration. The polyQ expansion makes Htt prone to aggregate and accumulate, and manipulations that mitigate protein misfolding or facilitate the clearance of misfolded proteins tend to slow disease progression in HD models. This article will focus on HD and the evidence that it is a conformational disease.
摘要
亨廷顿病（HD）是最常见的遗传性神经退行性疾病，其特征是运动不受控制地过度运动以及认知和情感缺陷。导致 HD 的突变导致亨廷顿蛋白（Htt）中的异常长聚谷氨酰胺（polyQ）扩展，该扩展赋予突变型 Htt 一种或多种毒性功能，导致神经退行性变。polyQ 扩展使 Htt 易于聚集和积累，并且减轻蛋白质错误折叠或促进错误折叠蛋白清除的操作往往会使 HD 模型中的疾病进展减缓。本文将重点介绍 HD 以及它是一种构象疾病的证据。
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Quantitative relationships between huntingtin levels, polyglutamine length, inclusion body formation, and neuronal death provide novel insight into huntington's disease molecular pathogenesis.亨廷顿病分子发病机制的新见解来自于对亨廷顿蛋白水平、多聚谷氨酰胺长度、包含体形成和神经元死亡之间定量关系的研究。
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Acute polyglutamine expression in inducible mouse model unravels ubiquitin/proteasome system impairment and permanent recovery attributable to aggregate formation.急性多聚谷氨酰胺表达在可诱导的小鼠模型中揭示了泛素/蛋白酶体系统损伤和归因于聚集体形成的永久性恢复。
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Balance between synaptic versus extrasynaptic NMDA receptor activity influences inclusions and neurotoxicity of mutant huntingtin.突触与突触外NMDA受体活性之间的平衡影响突变型亨廷顿蛋白的包涵体形成和神经毒性。
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Structure. 2009 Sep 9;17(9):1205-12. doi: 10.1016/j.str.2009.08.002.
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