MicroRNA-221 rescues the loss of dopaminergic neurons in a mouse model of Parkinson's disease.

Abstract

Parkinson's disease (PD) is one of the most common systemic neurodegenerative diseases and is related to the loss of dopaminergic neurons in the substantia nigra. Several studies verified that microRNA (miRNAs) targeting the Bim/Bax/caspase-3 signaling axis is involved in the apoptosis of dopaminergic neurons in substantia nigra. In this study, we aimedtoexploretheroleof miR-221 in PD. To examine the function of miR-221 in vivo, we used a well-established 6-OHDA-induced PD mouse model. Then we conducted adenovirus-mediated miR-221 overexpression in the PD mice. Our results showed that miR-221 overexpression improved motor behavior of the PD mice. We demonstrated that overexpression of miR-221 reduced the loss of dopaminergic neurons in the substantia nigra striatum by promoting their antioxidative and antiapoptosis capacities. Mechanistically, miR-221 targets Bim, thus inhibiting Bim and Bax caspase-3 mediated apoptosis signaling pathways. Our findings suggest miR-221 participates in the pathological process of PD and might be a potential drug target and provide new insight into PD treatment.