Metformin Ameliorates Aβ Pathology by Insulin-Degrading Enzyme in a Transgenic Mouse Model of Alzheimer’s Disease
Joint Authors
Tang, Ying
Zhang, Shi-Jie
Huang, Shun
Lu, Xinyi
Chen, Qu-Bo
Zhang, Dapeng
Li, Wanyan
Ao, Ran
Leung, Feona Chung-Yin
Zhang, Zhimin
Huang, Jisheng
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-04-21
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Alzheimer’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.
American Psychological Association (APA)
Lu, Xinyi& Huang, Shun& Chen, Qu-Bo& Zhang, Dapeng& Li, Wanyan& Ao, Ran…[et al.]. 2020. Metformin Ameliorates Aβ Pathology by Insulin-Degrading Enzyme in a Transgenic Mouse Model of Alzheimer’s Disease. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-10.
https://search.emarefa.net/detail/BIM-1203911
Modern Language Association (MLA)
Lu, Xinyi…[et al.]. Metformin Ameliorates Aβ Pathology by Insulin-Degrading Enzyme in a Transgenic Mouse Model of Alzheimer’s Disease. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-10.
https://search.emarefa.net/detail/BIM-1203911
American Medical Association (AMA)
Lu, Xinyi& Huang, Shun& Chen, Qu-Bo& Zhang, Dapeng& Li, Wanyan& Ao, Ran…[et al.]. Metformin Ameliorates Aβ Pathology by Insulin-Degrading Enzyme in a Transgenic Mouse Model of Alzheimer’s Disease. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-10.
https://search.emarefa.net/detail/BIM-1203911
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1203911