Small molecule oxidation products trigger disease-associated protein misfolding

被引：89

作者：

Bieschke, Jan ^{[1
]}

Zhang, Qinghai ^{[1
]}

Bosco, Daryl A. ^{[1
]}

Lerner, Richard A. ^{[1
]}

Powers, Evan T. ^{[1
]}

Wentworth, Paul, Jr. ^{[1
]}

Kelly, Jeffery W. ^{[1
]}

机构：

[1] Scripps Res Inst, La Jolla, CA 92037 USA

来源：

ACCOUNTS OF CHEMICAL RESEARCH | 2006年 / 39卷 / 09期

关键词：

D O I：

10.1021/ar0500766

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Oxidative stress and inflammation are risk factors for both the development of alpha-synucleinopathies, such as Parkinson's disease and dementia with Lewy bodies, and Alzheimer's disease, the two most common neurodegenerative disorders. These diseases are associated with the neurotoxic deposition of misassembled alpha-synuclein and amyloid-beta (A beta) peptides, respectively. Both occur sporadically, that is, without detectable disease-related mutations, in the vast majority of cases. Small molecule oxidation products, especially secosterols derived from cholesterol and 4-hydroxynonenal derived from lipid peroxidation, found in afflicted brains, accelerate the misassembly of both A beta and alpha-synuclein. This Account explores the mechanism of small molecule oxidation product-mediated protein misassembly and possible intervention strategies.

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页码：611 / 619

页数：9

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