机构：[1]Biological Resource Center, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China 广东省中医院[2]Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China 广东省中医院[3]Nanfang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, China [4]The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China [5]School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong [6]Drug Non-Clinical Evaluation Center of Guangzhou Institute of Pharmaceutical Industry, Guangzhou General Pharmaceutical Research Institute Co. Ltd., Guangzhou, China [7]School of Basic Medical Sciences, Center for Post-Doctoral Studies of Southern Medical University, Guangzhou, China [8]Post-Doctoral Research Center of Guangzhou Pharmaceutical Holdings Ltd., Guangzhou, China [9]The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
Alzheimer's disease (AD) is the most common neurodegenerative disease. The accumulation of amyloid beta (A beta) 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 A beta-induced pathology. Morris water maze and Y-maze results indicated that metformin could improve the learning and memory ability in APP(swe)/PS1(dE9) (APP/PS1) transgenic mice. F-18-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-1 beta and IL-6) in APP/PS1 mice. In addition, metformin obviously reduced the A beta level in the brain of APP/PS1 mice. Metformin did not affect the enzyme activities and mRNA expression levels of A beta-related secretases (ADAM10, BACE1, and PS1). Meanwhile, metformin also did not affect the mRNA expression levels of A beta-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.
基金：
Project of Administration of Traditional Chinese Medicine of Guangdong Province of China [20190408212815]
第一作者机构：[1]Biological Resource Center, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China [2]Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
共同第一作者：
通讯作者：
通讯机构：[6]Drug Non-Clinical Evaluation Center of Guangzhou Institute of Pharmaceutical Industry, Guangzhou General Pharmaceutical Research Institute Co. Ltd., Guangzhou, China [7]School of Basic Medical Sciences, Center for Post-Doctoral Studies of Southern Medical University, Guangzhou, China [8]Post-Doctoral Research Center of Guangzhou Pharmaceutical Holdings Ltd., Guangzhou, China
推荐引用方式(GB/T 7714)：
Lu Xin-Yi,Huang Shun,Chen Qu-Bo,et al.Metformin Ameliorates Aβ Pathology by Insulin-Degrading Enzyme in a Transgenic Mouse Model of Alzheimer's Disease[J].OXIDATIVE MEDICINE AND CELLULAR LONGEVITY.2020,2020:doi:10.1155/2020/2315106.
APA：
Lu, Xin-Yi,Huang, Shun,Chen, Qu-Bo,Zhang, Dapeng,Li, Wanyan...&Zhang, Shi-Jie.(2020).Metformin Ameliorates Aβ Pathology by Insulin-Degrading Enzyme in a Transgenic Mouse Model of Alzheimer's Disease.OXIDATIVE MEDICINE AND CELLULAR LONGEVITY,2020,
MLA：
Lu, Xin-Yi,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.(2020)
