BMSCs-exosomes containing GDF-15 alleviated SH-SY5Y cell injury model of Alzheimer's disease via AKT/GSK-3β/β-catenin.

Brain Research Bulletin
Wen-Ping XiongKui Liu


Mesenchymal stem cells (MSCs) therapy has great potential for Alzheimer's disease (AD) treatment. Here, we investigated the roles of BMSCs-exosomes containing growth differentiation factor-15 (GDF-15) in regulating SH-SY5Y cell injury in AD. The SH-SY5Y cell injury model was constructed by treating SH-SY5Y cells with 10 μM Aβ42. GDF-15 expression was assessed using qRT-PCR and western blot. CCK8 assay and flow cytometry assay were employed to elevate cell proliferation and apoptosis, respectively. The expression levels of inflammatory factors (IL-6, IL-1β, TNFα and IL-8) and Aβ42 were detected using ELISA. Besides, the levels of apoptosis-related proteins and AKT pathway-related proteins were determined using western blot. Our results displayed that BMSCs-EVs treatment elevated cell viability, while suppressed cell apoptosis and inflammation in Aβ42-treated SH-SY5Y cells. Exosomes secreted by BMSCs after GDF-15 silence lost the ability to restore Aβ42-induced SH-SY5Y cell damage. GDF-15 treatment restored Aβ42-induced SH-SY5Y cell damage, while it was eliminated by AKT pathway inhibition. BMSCs-exosomes containing GDF-15 upregulated NEP and IDE via activation of AKT/GSK-3β/β-catenin pathway, thereby degrading Aβ42 protein to re...Continue Reading

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Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis