Aggregation-defective α-synuclein mutants inhibit the fibrillation of Parkinson's disease-linked α-synuclein variants

被引：19

作者：

Koo, Hyun-Jung ^{[1
]}

Choi, Min Yeong ^{[1
]}

Im, Hana ^{[1
]}

机构：

[1] Sejong Univ, Dept Mol Biol, Seoul 143747, South Korea

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2009年 / 386卷 / 01期

关键词：

Conformational switch; Protein amyloid; Protein fibrils; Protein folding; alpha-Synuclein; ALZHEIMERS-DISEASE; BETA-SHEET; MUTATION; FIBRILS; E46K; NEURODEGENERATION; FIBRILLOGENESIS; FIBRILLIZATION; PATHOGENESIS; DUPLICATION;

D O I：

10.1016/j.bbrc.2009.06.002

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 comprises the fibrillar core of Lewy bodies, which is one of the histologically defining lesions of Parkinson's disease. Previously, we screened for alpha-synuclein substitution mutants that do not form fibrils. For preventative or therapeutic uses, it is essential to suppress the oligomerization/fibrillation of the wild-type and PD-linked alpha-synuclein proteins. Here we have examined the effects of fibrillation-retarded alpha-synuclein mutants on fibril formation by wild-type and PD-linked alpha-synuclein molecules. Six self-aggregation-defective alpha-synuclein mutants completely inhibit the fibrillation of both wild-type and Parkinson's disease-linked of alpha-synuclein variants. These results suggest future applications for gene therapy: the transplantation of a fibrillation-blocking mutant alpha-synuclein gene into individuals who carry an early-onset PD-associated alpha-synuclein allele. Short synthetic peptides derived from these mutant sequences may also serve as a lead compound for the development of therapeutics for Parkinson's disease. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：165 / 169

页数：5

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