MicroRNA-106b-containing extracellular vesicles affect autophagy of neurons by regulating CDKN2B in Parkinson’s disease

Abstract

Parkinson’s disease (PD) is the second most frequent neurodegenerative disorder, and autophagy dysfunction is involved in the pathogenesis of PD. Mesenchymal stem cells (MSC)-derived extracellular vesicles (EVs) have been established as an attractive therapeutic tool, since they can serve as biological nanoparticles with beneficial effects in PD. Herein, the study aimed to investigate the effects of EVs derived microRNA (miR)-106b on autophagy of neurons in PD. Following the development of a mouse model of PD, we conducted behavior test, TUNEL assay and HE staining to verify the success of modeling. Afterward, MSC-derived EVs were extracted and identified. In hippocampal tissues and neurons of PD mice, miR-106b was poorly expressed, while CDKN2B was highly expressed. miR-106b shuttled by MSC-derived EVs increased neuronal survival, autophagy, LC3II/LC3I ratio and Bcl-2 protein expression, while inhibited neuronal apoptosis and Bax expression in PD mice. It was also confirmed that CDKN2B is a downstream target of miR-106b. Overexpression of CDKN2B reversed the protective effects of miR-106b-containing EVs on neurons in mice with PD. Collectively, miR-106b-containing EVs alleviate neuronal apoptosis and enhance neuronal autophagy in PD by downregulating CDKN2B.