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Current understanding on the pathogenesis of polyglutamine diseases 被引量:2

多聚谷氨酰胺疾病分子发病机制的研究进展(英文)
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摘要 Polyglutamine (polyQ) diseases are a family of neurodegenerative disorders including Huntington’s disease, spinobulbar muscular atrophy,dentatorubral-pallidoluysian atrophy and several spinocerebellar ataxias.polyQ diseases are caused by abnormal expansion of CAG repeats in certain genes.The expanded CAG repeats are then translated into a series of abnormally expanded polyQ tracts.Such polyQ tracts may induce misfolding of the disease-causing proteins.The present review mainly focuses on the common characteristics of the pathogenesis of these polyQ diseases,including conformational transition of proteins and its influence on the function of these proteins,the correlation between decreased ability of proteoly-sis and late-onset polyQ diseases,and the relationship between wide expression of disease-causing proteins and selective neuronal death. 多聚谷氨酰胺疾病是一类中枢神经系统退行性疾病,目前已知的包括亨廷顿氏舞蹈病、脊延髓肌萎缩症、齿状核红核苍白球丘脑下部核萎缩以及其它几种脊髓小脑共济失调亚型。多聚谷氨酰胺疾病是由疾病相关基因的外显子内CAG三核苷酸重复序列异常扩展引起的,后者导致其编码的多聚谷氨酰胺链的异常延长,引起相关蛋白质的错误折叠。本文主要探讨多聚谷氨酰胺疾病分子发病机制的一些共同特征,包括蛋白质构象变化及其对蛋白功能的影响、蛋白水解能力下降与疾病迟发性的相互关系以及致病蛋白广泛表达与神经元选择性死亡的关系。
出处 《Neuroscience Bulletin》 SCIE CAS CSCD 2010年第3期247-256,共10页 神经科学通报(英文版)
基金 supported by the grants from the National Natural Science Foundation of China(No.30600197) the Specialized Research Fund for the Doctoral Program of Higher Education of China(No.20050285017)
关键词 POLYGLUTAMINE the central nervous system neurodegenerative diseases late-onset disorders UBIQUITIN autophagy 多聚谷氨酰胺 中枢神经系统 神经退行性疾病 迟发型障碍 泛素 自噬
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  • 1Orr HT, Zoghbi HY. Trinucleotide repeat disorders. Annu Rev Neurosci 2007, 30: 575-621.
  • 2Nagai Y, Inui T, Popiel HA, Fujikake N, Hasegawa K, Urade Y, etal. A toxic monomeric conformer of the polyglutamine protein. Nat Struct Mol Biol 2007, 14: 332-340.
  • 3Bevivino AE, Loll PJ. An expanded glutamine repeat destabilizes native ataxin-3 structure and mediates formation of parallel β-fibrils. Proc Natl Acad Sci U S A 2001, 98:11955-11960.
  • 4Chen S, Berthelier V, Hamilton JB, O'Nuallain B, Wetzel R. Amyloid-like features of polyglutamine aggregates and their assembly kinetics. Biochemistry 2002. 41: 7391-7399.
  • 5Marchut AJ, Hall CK. Spontaneous formation of annular structures observed in molecular dynamics simulations of polyglutamine peptides. Comput Biol Chem 2006, 30: 215-218.
  • 6Wacker JL, Zareie MH, Fong H, Sarikaya M, Muchowski PJ. Hsp70 and Hsp40 attenuate formation of spherical and annular polyglutamine oligomers by partitioning monomer. Nat Struct Mol Biol 2004, 11: 1215-1222.
  • 7Perutz MF, Finch JT, Berriman J, Lesk A. Amyloid fibers are water-filled nanotubes. Proc Natl Acad Sci U S A 2002, 99: 5591- 5595.
  • 8Khare SD, Ding F, Gwanmesia KN, Dokholyan NV. Molecular origin of polyglutamine aggregation in neurodegenerative diseases. PLoS Comput Biol 2005, 1: 230-235.
  • 9Zanuy D, Gunasekaran K, Lesk AM, Nussinov R. Computational study of the fibril organization of polyglutamine repeats reveals a common motif identified in β-helices. J Mol Biol 2006, 358: 330-345.
  • 10Marchut A J, Hall CK. Effects of chain length on the aggregation of model polyglutamine peptides: molecular dynamics simulations. Proteins 2007, 66: 96-109.

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