MicroRNA-214 participates in the neuroprotective effect of Resveratrol via inhibiting α-synuclein expression in MPTP-induced Parkinson's disease mouse.

Backgrounds and aims: MicroRNAs (miRNAs) have been reported to be involved in degenerative disorders including Parkinson's disease (PD). alpha-synuclein expression is strong associated with the pathogenesis of PD. In the present study, we investigated whether the regulation of alpha-synuclein expression by miR-214 is the potential mechanism underlying the neuroprotective effect of Resveratrol. Methods: The PD mouse model was established with the injection of MPTP (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and the human neuroblastoma cell line, SH-SY5Y, was administrated with MPP+. Results: The midbrain of PD mice and MPP+ treated SH-SY5Y cells had the lower expression levels of miR-214 and higher mRNA and protein expression of alpha-synuclein, which were reversed by Resveratrol administration. MiR-214 mimic down-regulated expression of alpha-synuclein and its 30-UTR activity, while the levels were up-regulated by miR-214 inhibitor. In addition, the cell viability, elevated by Resveratrol, was also decreased by miR-214 inhibitor or overexpressed alpha-synuclein. In vivo, miR-214 inhibitor down-regulated TH+ cells of ipsilateral and up-regulated alpha-synuclein expression compared with the group treated with Resveratrol. Conclusion: The loss of miR-214 in PD resulted in the increase of alpha-synuclein expression, which was the potential mechanism underlying the neuroprotective effects of Resveratrol. (C) 2015 Elsevier Masson SAS. All rights reserved.