Small extracellular vesicles from adipose derived stem cells alleviate microglia activation and improve motor deficit of Parkinson's disease via miR-100-5p/DTX3L/STAT1 signaling axis.

Dopaminergic neuron loss caused by microglia activation is an important pathological factor of Parkinson's disease (PD). Previously, we reported that small extracellular vesicle from adipose derived stem cells (ADSC-sEVs) could inhibit the activation of microglia and protect neuron apoptosis from microglia activation. However, whether ADSC-sEVs have protective effect on the motor deficit of PD mouse and the exact mechanism remains unknown. In this study, ADSC-sEVs were delivered to experimental model of Parkinson's disease by tail vein injection to explore the in vivo effect of ADSC-sEVs on PD. Next, the potential key microRNA in ADSC-sEVs was screened by RNA sequencing (RNA-seq), and the exact mechanism was further explored. We found that ADSC-sEVs greatly alleviated the activation of microglia and reduced the loss of dopaminergic neurons in the substantia nigra of PD mice, the motor deficit was also significantly improved. By RNA-seq analysis, miR-100-5p was verified as a potential microRNA in this process, because knockdown of miR-100-5p in ADSC-sEVs weakened the protective effect of ADSC-sEVs on PD mouse as well as the anti-inflammatory effect on microglia activation. Finally, we found that miR-100-5p could target Deltex E3 ubiquitin ligase 3 L (DTX3L) and suppress its expression, which then decreased the expression and phosphorylation of Signal Transducers and Activators of Transcription 1 (STAT1), as well as alleviating the activation of microglia. Our findings illustrate that ADSC-sEVs are an effective therapy for PD, and it could be a promising therapy for the treatment of PD.