title: Metformin Alleviated Aβ-Induced Apoptosis via the Suppression of JNK MAPK Signaling Pathway in Cultured Hippocampal Neurons.
abstract: Both diabetes and hyperinsulinemia are confirmed risk factors for Alzheimer's disease. Some researchers proposed that antidiabetic drugs may be used as disease-modifying therapies, such as metformin and thiazolidinediones, although more evidence was poorly supported. The aim of the current study is to investigate the role of metformin in Aβ-induced cytotoxicity and explore the underlying mechanisms. First, the experimental results show that metformin salvaged the neurons exposed to Aβ in a concentration-dependent manner with MTT and LDH assay. Further, the phosphorylation levels of JNK, ERK1/2, and p38 MAPK were measured with western blot analysis. It was investigated that Aβ increased phospho-JNK significantly but had no effect on phospho-p38 MAPK and phospho-ERK1/2. Metformin decreased hyperphosphorylated JNK induced by Aβ; however, the protection of metformin against Aβ was blocked when anisomycin, the activator of JNK, was added to the medium, indicating that metformin performed its protection against Aβ in a JNK-dependent way. In addition, it was observed that metformin protected the neurons via the suppression of apoptosis. Taken together, our findings demonstrate that metformin may have a positive effect on Aβ-induced cytotoxicity, which provides a preclinical strategy against AD for elders with diabetes.
authors.affiliation: Department of Endocrinology and Metabolism, General Hospital of Beijing Military Region, Beijing 100700, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.affiliation: Affiliated Hospital of Beijing Institute of Aeronautical Material, Beijing 100060, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Teng
authors.affiliation: Department of Endocrinology and Metabolism, General Hospital of Beijing Military Region, Beijing 100700, China.
authors.forename: Xingguang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology and Metabolism, General Hospital of Beijing Military Region, Beijing 100700, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Lv
authors.affiliation: Department of Neurobiology and Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China.
authors.forename: Yanling
authors.identifier: 0000-0003-1904-900X
authors.initials: Y
authors.lastname: Yin
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D048909:Diabetes Complications / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008687:Metformin / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D008687:Metformin; D048051:p38 Mitogen-Activated Protein Kinases