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: Kong J, Wan L, Wang Y, Zhang H, Zhang W
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Publicado: Dove Medical Press 2020
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spelling oai:doaj.org-article:f1c592ba597f4720ac5a9da19d0f0a5e2021-12-02T03:46:00ZLiraglutide Attenuates Aβ42 Generation in APPswe/SH-SY5Y Cells Through the Regulation of Autophagy1178-2021https://doaj.org/article/f1c592ba597f4720ac5a9da19d0f0a5e2020-07-01T00:00:00Zhttps://www.dovepress.com/liraglutide-attenuates-abeta42-generation-in-appswesh-sy5y-cells-throu-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Jingjing 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, JNKKong JWan LWang YZhang HZhang WDove Medical Pressarticlealzheimer’s diseaseglucagonlike peptide 1autophagyaβjnkNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 16, Pp 1817-1825 (2020)
institution DOAJ
collection DOAJ
language EN
topic alzheimer’s disease
glucagonlike peptide 1
autophagy

jnk
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
spellingShingle alzheimer’s disease
glucagonlike peptide 1
autophagy

jnk
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
Kong J
Wan L
Wang Y
Zhang H
Zhang W
Liraglutide Attenuates Aβ42 Generation in APPswe/SH-SY5Y Cells Through the Regulation of Autophagy
description 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
format article
author Kong J
Wan L
Wang Y
Zhang H
Zhang W
author_facet Kong J
Wan L
Wang Y
Zhang H
Zhang W
author_sort Kong J
title Liraglutide Attenuates Aβ42 Generation in APPswe/SH-SY5Y Cells Through the Regulation of Autophagy
title_short Liraglutide Attenuates Aβ42 Generation in APPswe/SH-SY5Y Cells Through the Regulation of Autophagy
title_full Liraglutide Attenuates Aβ42 Generation in APPswe/SH-SY5Y Cells Through the Regulation of Autophagy
title_fullStr Liraglutide Attenuates Aβ42 Generation in APPswe/SH-SY5Y Cells Through the Regulation of Autophagy
title_full_unstemmed Liraglutide Attenuates Aβ42 Generation in APPswe/SH-SY5Y Cells Through the Regulation of Autophagy
title_sort liraglutide attenuates aβ42 generation in appswe/sh-sy5y cells through the regulation of autophagy
publisher Dove Medical Press
publishDate 2020
url https://doaj.org/article/f1c592ba597f4720ac5a9da19d0f0a5e
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