PMID- 38229323 OWN - NLM STAT- MEDLINE DCOM- 20240118 LR - 20240118 IS - 1099-0461 (Electronic) IS - 1095-6670 (Linking) VI - 38 IP - 1 DP - 2024 Jan TI - miRNA-211-5p inhibition enhances the protective effect of hucMSC-derived exosome in Abeta(1-40) -induced SH-SY5Y cells by increasing NEP expression. PG - e23624 LID - 10.1002/jbt.23624 [doi] AB - 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 Abeta(1-40) . We observed that incubation with hucMSC-derived exosomes effectively protected SH-S5Y5 cells from Abeta(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 Abeta(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. CI - (c) 2023 The Authors. Journal of Biochemical and Molecular Toxicology published by Wiley Periodicals LLC. FAU - Chen, Huijing AU - Chen H AD - Central Laboratory, The Fifth Hospital of Xiamen, Xiamen, Fujian, China. FAU - Huang, Zhongqin AU - Huang Z AD - Department of Nursing, The Fifth Hospital of Xiamen, Xiamen, Fujian, China. FAU - Lei, Aidi AU - Lei A AD - Department of Neurology, The Fifth Hospital of Xiamen, Xiamen, Fujian, China. FAU - Yu, Xiaowen AU - Yu X AD - Department of Laboratory Medicine, Xiamen Medical College, Xiamen, Fujian, China. FAU - Shen, MeiLing AU - Shen M AD - Department of Laboratory Medicine, Xiamen Medical College, Xiamen, Fujian, China. FAU - Wu, Dan AU - Wu D AUID- ORCID: 0009-0007-9693-1588 AD - Central Laboratory, The Fifth Hospital of Xiamen, Xiamen, Fujian, China. AD - Xiamen Key Laboratory of Precision Diagnosis and Treatment of Chronic Kidney Disease, Xiamen, Fujian, China. LA - eng GR - 2021D013/Science and Technology Plan Project of Fujian Province/ GR - 3502Z20214ZD1266/Xiamen Medical and Health Guidance Project/ PT - Journal Article PL - United States TA - J Biochem Mol Toxicol JT - Journal of biochemical and molecular toxicology JID - 9717231 RN - 0 (MicroRNAs) RN - 0 (MIRN211 microRNA, human) SB - IM MH - Humans MH - *Exosomes/metabolism MH - *Neuroblastoma/metabolism MH - *MicroRNAs/genetics/metabolism MH - *Mesenchymal Stem Cells/metabolism MH - *Alzheimer Disease/therapy/metabolism MH - Umbilical Cord/metabolism OTO - NOTNLM OT - Alzheimer's disease OT - human umbilical cord mesenchymal stem cell-exosomes OT - microRNA-211-5p inhibitor OT - neprilysin EDAT- 2024/01/17 06:42 MHDA- 2024/01/18 06:42 CRDT- 2024/01/17 01:03 PHST- 2023/10/24 00:00 [revised] PHST- 2023/04/17 00:00 [received] PHST- 2023/12/14 00:00 [accepted] PHST- 2024/01/18 06:42 [medline] PHST- 2024/01/17 06:42 [pubmed] PHST- 2024/01/17 01:03 [entrez] AID - 10.1002/jbt.23624 [doi] PST - ppublish SO - J Biochem Mol Toxicol. 2024 Jan;38(1):e23624. doi: 10.1002/jbt.23624.