Liraglutide Attenuates Aβ42 Generation in APPswe/SH-SY5Y Cells Through the Regulation of Autophagy
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 Med...
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| Autores principales: | , , , , |
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2020
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| Acceso en línea: | https://doaj.org/article/f1c592ba597f4720ac5a9da19d0f0a5e |
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| Sumario: | 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 +86-18098875886Email jingjingeasy@126.comObjective: 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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