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

Background: 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.

Methods: 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.

Results: 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 relieve SH-SY5Y cell damage.

Conclusion: BMSCs-exosomes containing GDF-15 alleviated SH-SY5Y cell damage via AKT/GSK-3β/β-catenin. Our work confers a promising therapeutic strategy for AD.