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Article: Metformin Ameliorates Aβ Pathology by Insulin-Degrading Enzyme in a Transgenic Mouse Model of Alzheimer's Disease

TitleMetformin Ameliorates Aβ Pathology by Insulin-Degrading Enzyme in a Transgenic Mouse Model of Alzheimer's Disease
Authors
Issue Date2020
PublisherHindawi Publishing Corporation. The Journal's web site is located at http://www.hindawi.com/journals/oximed/
Citation
Oxidative Medicine and Cellular Longevity, 2020, v. 2020, article no. 2315106 How to Cite?
AbstractAlzheimer’s disease (AD) is the most common neurodegenerative disease. The accumulation of amyloid beta (Aβ) is the main pathology of AD. Metformin, a well-known antidiabetic drug, has been reported to have AD-protective effect. However, the mechanism is still unclear. In this study, we tried to figure out whether metformin could activate insulin-degrading enzyme (IDE) to ameliorate Aβ-induced pathology. Morris water maze and Y-maze results indicated that metformin could improve the learning and memory ability in APPswe/PS1dE9 (APP/PS1) transgenic mice. 18F-FDG PET-CT result showed that metformin could ameliorate the neural dysfunction in APP/PS1 transgenic mice. PCR analysis showed that metformin could effectively improve the mRNA expression level of nerve and synapse-related genes (Syp, Ngf, and Bdnf) in the brain. Metformin decreased oxidative stress (malondialdehyde and superoxide dismutase) and neuroinflammation (IL-1β and IL-6) in APP/PS1 mice. In addition, metformin obviously reduced the Aβ level in the brain of APP/PS1 mice. Metformin did not affect the enzyme activities and mRNA expression levels of Aβ-related secretases (ADAM10, BACE1, and PS1). Meanwhile, metformin also did not affect the mRNA expression levels of Aβ-related transporters (LRP1 and RAGE). Metformin increased the protein levels of p-AMPK and IDE in the brain of APP/PS1 mice, which might be the key mechanism of metformin on AD. In conclusion, the well-known antidiabetic drug, metformin, could be a promising drug for AD treatment.
Persistent Identifierhttp://hdl.handle.net/10722/288530
ISSN
2019 Impact Factor: 5.076
2015 SCImago Journal Rankings: 1.503
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLu, XY-
dc.contributor.authorHuang, S-
dc.contributor.authorChen, QB-
dc.contributor.authorZhang, D-
dc.contributor.authorLi, W-
dc.contributor.authorAo, R-
dc.contributor.authorLeung, FCY-
dc.contributor.authorZhang, Z-
dc.contributor.authorHuang, J-
dc.contributor.authorTang, Y-
dc.contributor.authorZhang, SJ-
dc.date.accessioned2020-10-07T02:01:03Z-
dc.date.available2020-10-07T02:01:03Z-
dc.date.issued2020-
dc.identifier.citationOxidative Medicine and Cellular Longevity, 2020, v. 2020, article no. 2315106-
dc.identifier.issn1942-0900-
dc.identifier.urihttp://hdl.handle.net/10722/288530-
dc.description.abstractAlzheimer’s disease (AD) is the most common neurodegenerative disease. The accumulation of amyloid beta (Aβ) is the main pathology of AD. Metformin, a well-known antidiabetic drug, has been reported to have AD-protective effect. However, the mechanism is still unclear. In this study, we tried to figure out whether metformin could activate insulin-degrading enzyme (IDE) to ameliorate Aβ-induced pathology. Morris water maze and Y-maze results indicated that metformin could improve the learning and memory ability in APPswe/PS1dE9 (APP/PS1) transgenic mice. 18F-FDG PET-CT result showed that metformin could ameliorate the neural dysfunction in APP/PS1 transgenic mice. PCR analysis showed that metformin could effectively improve the mRNA expression level of nerve and synapse-related genes (Syp, Ngf, and Bdnf) in the brain. Metformin decreased oxidative stress (malondialdehyde and superoxide dismutase) and neuroinflammation (IL-1β and IL-6) in APP/PS1 mice. In addition, metformin obviously reduced the Aβ level in the brain of APP/PS1 mice. Metformin did not affect the enzyme activities and mRNA expression levels of Aβ-related secretases (ADAM10, BACE1, and PS1). Meanwhile, metformin also did not affect the mRNA expression levels of Aβ-related transporters (LRP1 and RAGE). Metformin increased the protein levels of p-AMPK and IDE in the brain of APP/PS1 mice, which might be the key mechanism of metformin on AD. In conclusion, the well-known antidiabetic drug, metformin, could be a promising drug for AD treatment.-
dc.languageeng-
dc.publisherHindawi Publishing Corporation. The Journal's web site is located at http://www.hindawi.com/journals/oximed/-
dc.relation.ispartofOxidative Medicine and Cellular Longevity-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleMetformin Ameliorates Aβ Pathology by Insulin-Degrading Enzyme in a Transgenic Mouse Model of Alzheimer's Disease-
dc.typeArticle-
dc.identifier.emailLeung, FCY: feonalcy@hku.hk-
dc.identifier.authorityLeung, FCY=rp02269-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1155/2020/2315106-
dc.identifier.pmid32377293-
dc.identifier.pmcidPMC7191377-
dc.identifier.scopuseid_2-s2.0-85084393845-
dc.identifier.hkuros314779-
dc.identifier.volume2020-
dc.identifier.spagearticle no. 2315106-
dc.identifier.epagearticle no. 2315106-
dc.identifier.isiWOS:000531637500001-
dc.publisher.placeUnited States-

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