TY - JOUR T1 - Mesenchymal stem cells-derived extracellular vesicles ameliorate Alzheimer's disease in rat models via the microRNA-29c-3p/BACE1 axis and the Wnt/β-catenin pathway. AU - Sha,Sha, AU - Shen,Xueli, AU - Cao,Yunpeng, AU - Qu,Le, Y1 - 2021/06/04/ PY - 2020/09/21/received PY - 2021/04/29/accepted PY - 2021/6/5/pubmed PY - 2021/7/22/medline PY - 2021/6/4/entrez KW - Alzheimer's disease KW - BACE1 KW - bone marrow mesenchymal stem cells KW - extracellular vesicles KW - microRNA-29c-3p SP - 15285 EP - 15306 JF - Aging JO - Aging (Albany NY) VL - 13 IS - 11 N2 - Currently, Alzheimer's disease (AD) cannot be treated effectively. Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) (MSC-EVs) exhibit therapeutic effects on many diseases. This study investigated the mechanism of bone marrow MSC-EVs (BM-MSC-EVs) in a rat model of AD. The cognitive function, amyloid-β (Aβ) plaques, Aβ deposition areas and levels of Aβ1-42, Aβ decomposition-related factors (NEP and IDE), and inflammatory cytokines in BM-MSC-EVs-treated AD rats were measured. The effect of BM-MSC-EVs was studied in AD neuron model. microRNA (miR)-29c-3p and BACE1 expression, as well as levels of Wnt/β-catenin pathway-related factors in AD and EVs-treated AD models were detected. miR-29c-3p relationship with BACE1 was predicted and confirmed. miR-29c-3p and BACE1 were interfered to verify the mechanism of EVs in AD. The Wnt/β-catenin pathway inhibitor DKK1 was further added to EVs-treated AD neurons. BM-MSC-EVs showed therapeutic effects on AD rats and neurons. BM-MSC-EVs carried miR-29c-3p into AD neurons. miR-29c-3p targeted BACE1. Silencing miR-29c-3p in BM-MSCs reduced BM-MSC-EV therapeutic effect on AD, which was reversed after BACE1 knockdown. miR-29c-3p targeted BACE1 and activated the Wnt/β-catenin pathway, and the Wnt/β-catenin pathway inhibition impaired EV therapeutic effects on AD. We highlighted that BM-MSC-EVs delivered miR-29c-3p to neurons to inhibit BACE1 expression and activate the Wnt/β-catenin pathway, thereby playing a therapeutic role in AD. This study may provide a novel perspective for elucidating the mechanism of MSCs in the treatment of AD. SN - 1945-4589 UR - https://www.unboundmedicine.com/medline/citation/34086603/Mesenchymal_stem_cells_derived_extracellular_vesicles_ameliorate_Alzheimer's_disease_in_rat_models_via_the_microRNA_29c_3p/BACE1_axis_and_the_Wnt/β_catenin_pathway_ DB - PRIME DP - Unbound Medicine ER -