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延伸酶——神经紊乱相关的新角色。

Elongator - an emerging role in neurological disorders.

机构信息

Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research), University of Liège, C.H.U. Sart Tilman, Liège, Belgium.

出版信息

Trends Mol Med. 2010 Jan;16(1):1-6. doi: 10.1016/j.molmed.2009.11.002. Epub 2009 Dec 23.

Abstract

Neurological disorders are becoming a major public health issue in our aging society. An important objective is to understand the molecular events that underlie these diseases to prevent their onset and/or halt their progression. Acetylation of alpha-tubulin is a post-translational modification of microtubules that serves as a recognition signal for the anchoring of molecular motors and, as such, underlies the transport of various proteins or organelles in neurons. This process is affected in striatal and cortical neurons from Huntington's disease patients. Recent studies have shown that Elp3, the catalytic subunit of the Elongator complex, promotes the acetylation of alpha-tubulin in microtubules. Elongator complex activity is impaired in patients with familial dysautonomia. Based on converging experimental and clinical evidence, we propose that Elongator might be commonly targeted in different neurological disorders, and thus might represent a strong candidate for research and development efforts to design drug-based therapies.

摘要

神经紊乱在老龄化社会已成为主要的公共健康问题。一个重要的目标是理解这些疾病的分子事件,以预防其发生和/或阻止其进展。α-微管蛋白乙酰化是微管的一种翻译后修饰,作为分子马达锚定的识别信号,从而为各种蛋白质或细胞器在神经元中的运输提供基础。这个过程受到亨廷顿氏病患者纹状体和皮质神经元的影响。最近的研究表明,Elongator 复合物的催化亚基 Elp3 促进微管中的α-微管蛋白乙酰化。家族性自主神经异常患者的 Elongator 复合物活性受损。基于趋同的实验和临床证据,我们提出 Elongator 可能在不同的神经紊乱中被共同靶向,因此可能代表着一个强有力的候选药物研发靶点。

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