Lipid peroxidation is essential for α-synuclein-induced cell death

被引：133

作者：

Angelova, Plamena R. ^{[1
]}

Horrocks, Mathew H. ^{[2
]}

Klenerman, David ^{[2
]}

Gandhi, Sonia ^{[1
]}

Abramov, Andrey Y. ^{[1
]}

Shchepinov, Mikhail S. ^{[3
]}

机构：

[1] UCL Inst Neurol, London WC1N 3BG, England

[2] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England

[3] Retrotope Inc, Los Altos Hills, CA USA

来源：

JOURNAL OF NEUROCHEMISTRY | 2015年 / 133卷 / 04期

关键词：

deuterated PUFA; lipid peroxidation; oxidative stress; alpha-synuclein; POLYUNSATURATED FATTY-ACIDS; OXIDATIVE STRESS; MODEL;

D O I：

10.1111/jnc.13024

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Parkinson's disease is the second most common neurodegenerative disease and its pathogenesis is closely associated with oxidative stress. Deposition of aggregated alpha-synuclein (alpha-Syn) occurs in familial and sporadic forms of Parkinson's disease. Here, we studied the effect of oligomeric alpha-Syn on one of the major markers of oxidative stress, lipid peroxidation, in primary co-cultures of neurons and astrocytes. We found that oligomeric but not monomeric alpha-Syn significantly increases the rate of production of reactive oxygen species, subsequently inducing lipid peroxidation in both neurons and astrocytes. Pre-incubation of cells with isotope-reinforced polyunsaturated fatty acids (D-PUFAs) completely prevented the effect of oligomeric alpha-Syn on lipid peroxidation. Inhibition of lipid peroxidation with D-PUFAs further protected cells from cell death induced by oligomeric alpha-Syn. Thus, lipid peroxidation induced by misfolding of alpha-Syn may play an important role in the cellular mechanism of neuronal cell loss in Parkinson's disease.

引用

页码：582 / 589

页数：8

共 30 条

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