Abstract

α-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 α-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 α-synuclein protein levels through the 3′-untranslated region (UTR) of α-synuclein mRNA. Importantly, miR-7-induced down-regulation of α-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 α-synuclein expression. These findings provide a mechanism by which α-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 α-synucleinopathies.

Keywords

SynucleinopathiesAlpha-synucleinmicroRNABiologyDopaminergicNeurotoxinCell biologySynucleinUntranslated regionMPTPParkinson's diseaseTransgeneOxidative stressMolecular biologyMessenger RNADopamineNeuroscienceGeneEndocrinologyInternal medicineGeneticsMedicineDisease

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Publication Info

Year
2009
Type
article
Volume
106
Issue
31
Pages
13052-13057
Citations
618
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Eunsung Junn, Kang‐Woo Lee, Byeong Seon Jeong et al. (2009). Repression of α-synuclein expression and toxicity by microRNA-7. Proceedings of the National Academy of Sciences , 106 (31) , 13052-13057. https://doi.org/10.1073/pnas.0906277106

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DOI
10.1073/pnas.0906277106