Objective: This study aimed to clarify whether liraglutide, a GLP-1 analogue, can ameliorate Aβ pathology through the regulation of autophagy in Alzheimer’s disease (AD) and to explore the related mechanisms thereof.
Methods: We used SH-SY5Y cells transiently transfected with APP695swe plasmid as an AD cellular model. Transfected cells were treated with liraglutide for 24 h in the presence or absence of 3-MA. Autophagy markers and the Aβ level were then evaluated by Western blot and ELISA. We also investigated the potential involvement of mTOR and JNK pathway in liraglutide-mediated autophagy.
Results: Our results showed that liraglutide reduced Aβ 42 generation and enhanced autophagy in APPswe/SH-SY5Y cells; however, these effects could be counteracted with 3-MA. Furthermore, our data showed that liraglutide-induced autophagy does not follow the mTOR pathway. Liraglutide might promote autophagy in APPswe/SH-SY5Y cells by activating the JNK pathway and inhibiting the beclin-1/bcl-2 complex.
Conclusion: Here, we report a novel mechanism underlying liraglutide-attenuated Aβ 42 generation through the activation of autophagy in AD cellular model.
Keywords: Alzheimer’s disease, glucagonlike peptide 1, autophagy, Aβ, JNK