Semaglutide-mediated protection against Aβ correlated with enhancement of autophagy and inhibition of apotosis.

BACKGROUND: Semaglutide, a glucagon-like peptide-1 (GLP-1) analogue with an extended half-life of approximately 1 week has being come into clinic trial to treat parkingson's disease but little is known about its effect to prevent against Alzheimer's disease (AD). The goal of the present study was to explore the potential mechanisms of semaglutide to protect against AD. METHODS: We treated SH-SY5Y cell line with Aβ as an AD model. Further, SH-SY5Y cells damaged by Aβ were treated by semaglutide. Autophagy-related proteins and apoptosis-related proteins were measured to explore molecular mechanisms for semaglutide to protect against Aβ. RESULTS: Semaglutide enhanced autophagy by increasing the expression of LC3II, Atg7, Beclin-1 and P62 which were inhibited by Aβ. Further we showed that semaglutide inhibited apoptosis by inhibiting the expression of Bax induced by Aβ and increasing the expression of Bcl2 inhibited by Aβ. CONCLUSION: Our results provide a clue for the hypothesis that autophagy enhancement and apoptosis inhibition may be involved in the effect of semaglutide to protect against Aβ .