circSAMD4A participates in the apoptosis and autophagy of dopaminergic neurons via the miR-29c-3p-mediated AMPK/mTOR pathway in Parkinson's disease

Parkinson's disease (PD) can lead to movement injury and cognitive dysfunction. Although advances have been made in attenuating PD, the effect of inhibiting the development of PD remains disappointing. Therefore, the present study aimed at investigating the etiology of Parkinson's disease and developing an alternative therapeutic strategy for patients with PD. A PD mouse model was established using an intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP-HCl; 30 mg/kg/day for 5 days), and a PD cellular model was established by treating SH-SY5Y cells with different concentrations of 1-methyl-4-phenylpyridinium (MPP+) for 24 h. The expression levels of circular RNA sterile alpha motif domain containing 4A (circSAMD4A) and microRNA (miR)-29c-3p in both midbrain tissues and SH-SY5Y cells were detected via reverse transcription-quantitative PCR. The interaction between circSAMD4A and miR-29c-3p was verified using a dual-luciferase reporter experiment. Apoptosis-, autophagy- and 5 ' AMP-activated protein kinase (AMPK)/mTOR cascade-associated proteins in midbrain tissues and SH-SY5Y cells were detected using western blotting. Furthermore, TUNEL staining and flow cytometry were used to analyze cell apoptosis. It was found that circSAMD4A was upregulated, while miR-29c-3p was downregulated in both PD animal and cellular models. Moreover, circSAMD4A directly targeted and negatively regulated miR-29c-3p. Further studies identified that circSAMD4A knockdown inhibited MPTP- or MPP+-induced apoptosis and autophagy; however, these effects were abolished by an miR-29c-3p inhibitor. In addition, circSAMD4A knockdown repressed phosphorylated-AMPK expression and increased mTOR expression in MPTP- or MPP+-induced PD models, the effects of which were reversed by a miR-29c-3p inhibitor. Collectively, these results suggested that circSAMD4A participated in the apoptosis and autophagy of dopaminergic neurons by modulating the AMPK/mTOR cascade via miR-29c-3p in PD.

Automated summary

This study investigated the pathogenesis of Parkinson's disease and identified that circSAMD4A modulates apoptosis and autophagy of dopaminergic neurons through the AMPK/mTOR cascade via miR-29c-3p in PD.