miR-132-5p regulates apoptosis and autophagy in MPTP model of Parkinson’s disease by targeting ULK1
Jianli Zhao, Manyi Yang, Qi Li, Xiaorui Pei, Xiaodong Zhu
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder that is characterized by a loss of dopaminergic neurons in the substantia nigra of the brain. Numerous investigations have focused on the underlying mechanism involved in the progression of PD in recent decades. miR-132 is abnormal expression in many diseases including PD. However, the functional role and molecular mechanism of miR-132-5p in PD pathogenesis are still not elucidated. In our study, we found miR-132-5p was upregulated in 1-methyl-4-pheny-1,2,3,6-tetrahydropyridine (MPTP) model of PD. MTT assay and flow cytometric analysis revealed that inhibition of miR-132-5p increased cell survival ability and reduced MPTP-induced apoptosis of SH-SY5Y cells. Furthermore, inhibition of miR-132-5p could significantly suppressed mRNA and protein expression levels of LC3 and Beclin 1, indicating inhibition of miR-132-5p might restrain autophagy in PD. Subsequently, ULK1 was identified as a target of miR-132-5p and positively regulated by miR-132-5p at both mRNA and protein levels. Additionally, ectopic expression of ULK1 was able to reverse the effects of miR-132-5p inhibition. Taken together, our results demonstrated that miR-132-5p inhibition might exert a protective role in MPTP-treated PD models by targeting ULK1, indicating that miR-132-5p may be a prospective therapeutic target for PD.