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Liraglutide Attenuates Aβ42 Generation in APPswe/SH-SY5Y Cells Through the Regulation of Autophagy
Authors Kong J, Wan L, Wang Y, Zhang H, Zhang W
Received 27 April 2020
Accepted for publication 28 June 2020
Published 27 July 2020 Volume 2020:16 Pages 1817—1825
DOI https://doi.org/10.2147/NDT.S260160
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Yuping Ning
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 work
Correspondence: Jingjing Kong Tel +86-18098875886
Email [email protected]
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
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