miR-124 regulates cell apoptosis and autophagy in dopaminergic neurons and protects them by regulating AMPK/mTOR pathway in Parkinson’s disease

摘要

The important roles of miR-124 in the development and progression of various diseases are being increasing recognized. This study was aimed to investigate the potential roles of miR-124 in dopaminergic (DA) neuronal apoptosis and autophagy in Parkinson’s disease (PD) and to explore their mechanisms. Human SH-SY5Y cells that are treated with MPTP were transfected with mature miR-124 vector and control empty vector. The effect of MPTP on miR-124 mRNA level was analyzed using RT-PCR analysis. Furthermore, the effects of miR-124 expression on neuronal apoptosis and autophagy, as well as the expression of proteins in the AMPK/mTOR pathway, were analyzed using RT-PCR and western blotting. This study found that miR-124 was down-regulated in the MPTP-treated (100 μM) neurons, and miR-124 suppression significantly increased cell apoptosis and induced autophagy-associated protein expression, including that of Beclin 1 and increased the ratio of LC3 II/LC3 I compared with that in controls. In addition, in vitro rescue of miR-124 significantly decreased the percentage of apoptotic cells and the ratio of LC3 II/LC3 I, findings that were approximately equal to the controls. Moreover, miR-124 suppression increased p-AMPK but decreased p-mTOR levels in neurons. Our study suggested that miR-124 functions as a protector of DA neurons during PD through the involvement of cell apoptosis and autophagy by regulating the AMPK/mTOR pathway.