Effects of the mutations Ala30 to Pro and Ala53 to Thr on the physical and morphological properties of α-synuclein protein implicated in Parkinson's disease

被引：240

作者：

El-Agnaf, OMA

Jakes, R

Curran, MD

Wallace, A

机构：

[1] Queens Univ Belfast, Sch Biol & Biochem, Ctr Peptide & Prot Engn, Belfast BT9 7BL, Antrim, North Ireland

[2] MRC, Mol Biol Lab, Cambridge CB2 2QH, England

[3] Belfast City Hosp, No Ireland Histocompatibil & Immunogenet Lab, Belfast BT9 7AB, Antrim, North Ireland

来源：

FEBS LETTERS | 1998年 / 440卷 / 1-2期

基金：

英国医学研究理事会;

关键词：

alpha-synuclein; Parkinson's disease; Lewy body; self-aggregation; amyloid; neurodegenerative disease;

D O I：

10.1016/S0014-5793(98)01419-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

alpha-Synuclein (alpha-syn) protein has been found in association with the pathological lesions of a number of neurodegenerative diseases. Recently, mutations in the alpha-syn gene have been reported in families susceptible to an inherited form of Parkinson's disease. We report here that human wildtype alpha-syn, PD-linked mutant alpha-syn(Ala30Pro) and mutant alpha-syn(Ala53Thr) proteins can self-aggregate and form amyloid-like filaments. The mutant alpha-syn forms more beta-sheet and mature filaments than the wild-type protein. These findings suggest that accumulation of alpha-syn as insoluble deposits of amyloid may play a major role in the pathogenesis of these neurodegenerative diseases. (C) 1998 Federation of European Biochemical Societies.

引用

页码：67 / 70

页数：4

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