Abstract: Objective To investigate the protective effects of dulaglutide on Alzheimer’s disease (AD) - like neurodegenerative changes and its mechanism thereof. Methods Dulaglutide，a new drug for diabetes, was applied to observe and explore AD-like neurodegenerative changes induced by PI3K inhibitor wortmannin in SH-SY5Y cells. MTT assay was used to observe the cell vitality induced by dulaglutide, wortmannin and glucagon-like peptide (GLP-1) 1 receptor antagonist ex9-39. Western blot assay was used to detect the levels of phosphorylated Tau, neurofilaments (NFs) and the proteins of PI3K/GSK-3β signaling pathway. Results Dulaglutide improved the impaired vitality, increased the levels of phosphorylated PI3K and GSK-3β and decreased phosphorylation levels of tau and NFs induced by wortmannin in SHSY5Y cells. Ex9-39 antagonized the effects of Dulaglutide. Conclusion Dulaglutide protects SH-SY5Y cells from ADlike neurodegenerative changes through improving PI3K /GSK-3β insulin signaling pathway.

Key words: Alzheimer disease, glucagon-like peptide 1, 1-phosphatidylinositol 3-kinase, tau proteins, dulaglutide, insulin signaling pathway