miRNA-211-5p inhibition enhances the protective effect of hucMSC-derived exosome in Aß1-40 -induced SH-SY5Y cells by increasing NEP expression.

ABSTRACT

Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) could alleviate Alzheimer's disease (AD) defects. Additionally, engineered exosomes are more effective in treating diseases. In this study, we established an in vitro model of AD by treating SH-SY5Y cells with Aß1-40 . We observed that incubation with hucMSC-derived exosomes effectively protected SH-S5Y5 cells from Aß1-40 -induced damage. Since NEP plays a central role in suppressing AD development, we screened NEP-targeting miRNAs that are differentially expressed in control and AD patients. We identified miR-211-5p as a potent repressor of NEP expression. Exosomes purified from hucMSCs overexpressing miR-211-5p inhibitor exhibited significantly greater efficiency than control exosomes in mitigating the injury caused by Aß1-40 treatment. However, this enhanced protective effect was nullified by the knockdown of NEP. These observations demonstrate that inhibition of miR-211-5p has the potential to improve the efficacy of hucMSC-derived exosomes in AD treatment by increasing NEP expression.