Liraglutide Attenuates Aβ42 Generation in APPswe/SH-SY5Y Cells Through the Regulation of Autophagy

• Main Authors: Kong J, Wan L, Wang Y, Zhang H, Zhang W
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-07-01
• Series: Neuropsychiatric Disease and Treatment
• Subjects: alzheimer’s disease; glucagonlike peptide 1; autophagy; aβ; jnk
• Online Access: https://www.dovepress.com/liraglutide-attenuates-abeta42-generation-in-appswesh-sy5y-cells-throu-peer-reviewed-article-NDT

Jingjing Kong,1,* Liping Wan,2,* Yanfu Wang,1 Hua Zhang,1 Wei Zhang1 1Department of Geriatrics, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, People’s Republic of China; 2Department of Clinical Laboratory, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingjing Kong Tel [phone]Email [e-mail]: 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