miRNA‐211‐5p inhibition enhances the protective effect of hucMSC‐derived exosome in Aβ<sub>1‐40</sub>‐induced SH‐SY5Y cells by increasing NEP expression
Huijing Chen, Zhongqin Huang, Aidi Lei, X P Yu, MeiLing Shen, Dan Wu
Abstract
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 Aβ 1‐40 . We observed that incubation with hucMSC‐derived exosomes effectively protected SH‐S5Y5 cells from Aβ 1‐40 ‐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 Aβ 1‐40 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.