MicroRNA-494 reduces DJ-1 expression and exacerbates neurodegeneration

Abstract

Oxidative stress is believed to be a significant cause of Parkinson's disease (PD). DJ-1 is thought to be an oxidative sensor that protects cells from oxidative insult. It was reported that the level of total DJ-1 protein was significantly reduced in the substantia nigra of sporadic PD patients, suggesting that abnormal DJ-1 expression might contribute to PD pathogenesis. However, the molecular mechanisms underlying the regulation of DJ-1 expression are still not fully explored. As a post-transcriptional regulation of target gene expression, the roles of microRNAs in development and disease progression have received widespread concerns. Therefore, we hypothesized that microRNAs might participate in the regulation of the DJ-1 expression. In the present study, we found that miR-494 could bind to the 3'UTR of DJ-1. Overexpression of miR-494 significantly decreased the level of DJ-1 in vitro and rendered cells more susceptible to oxidative stress. In a MPTP mouse model, overexpression of miR-494 negatively regulated DJ-1 levels and exacerbated MPTP-induced neurodegeneration, as illustrated by the loss of dopaminergic neurons. In conclusion, upregulation of miR-494 contributed to oxidative stress induced neuronal death by inhibiting expression of DJ-1.

Keywords: DJ-1; Oxidative stress; Parkinson's disease; miR-494.