α-synuclein adopts an α-helical conformation in the presence of polyunsaturated fatty acids to hinder micelle formation

被引：73

作者：

Broersen, Kerensa ^{[1
]}

van den Brink, Daan ^{[1
]}

Fraser, Graham ^{[1
]}

Goedert, Michel ^{[1
]}

Davletov, Bazbek ^{[1
]}

机构：

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

来源：

BIOCHEMISTRY | 2006年 / 45卷 / 51期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1021/bi061743l

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 is a small cytosolic protein involved in the pathogenesis of Parkinson's disease and other neurodegenerative disorders. Recent studies suggested a lipid-related function for this brain-enriched protein. Since the brain carries a high level of docosahexaenoic acid (DHA) and since the extent of alpha-synuclein gene expression increases in response to DHA intake, we have investigated the interaction of alpha-synuclein with this essential omega-3 fatty acid. We show that alpha-synuclein allows DHA to be present in a soluble rather than micellar form. Upon interaction with DHA, the normally unstructured alpha-synuclein rapidly adopts an alpha-helical conformation. Prolonged exposure to DHA, however, gradually converts alpha-synuclein into amyloid-like fibrils. These results identify a potential biological function for alpha-synuclein and define an omega-3-linked pathway leading to alpha-synuclein aggregation.

引用

页码：15610 / 15616

页数：7

共 64 条

[1]

Adibhatla RM, 2006, AAPS J, V8, pE314

[2]

Baba M, 1998, AM J PATHOL, V152, P879

[3] Oxidative stress and arachidonic acid mobilization [J].