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标题：Repression of α-synuclein expression and toxicity by microRNA-7
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作者：Eunsung Junn ; Kang-Woo Lee ; Byeong Seon Jeong 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：31
页码：13052-13057
DOI：10.1073/pnas.0906277106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：{alpha} -Synuclein is a key protein in Parkinson's disease (PD) because it accumulates as fibrillar aggregates in pathologic hallmark features in affected brain regions, most notably in nigral dopaminergic neurons. Intraneuronal levels of this protein appear critical in mediating its toxicity, because multiplication of its gene locus leads to autosomal dominant PD, and transgenic animal models overexpressing human {alpha}-synuclein manifest impaired function or decreased survival of dopaminergic neurons. Here, we show that microRNA-7 (miR-7), which is expressed mainly in neurons, represses {alpha}-synuclein protein levels through the 3'-untranslated region (UTR) of {alpha}-synuclein mRNA. Importantly, miR-7-induced down-regulation of {alpha}-synuclein protects cells against oxidative stress. Further, in the MPTP-induced neurotoxin model of PD in cultured cells and in mice, miR-7 expression decreases, possibly contributing to increased {alpha}-synuclein expression. These findings provide a mechanism by which {alpha}-synuclein levels are regulated in neurons, have implications for the pathogenesis of PD, and suggest miR-7 as a therapeutic target for PD and other {alpha}-synucleinopathies.
关键词：Parkinson's disease ; neuroprotection ; MPTP model ; microRNA