TY - JOUR A2 - Srivastava, Amit K. AU - Chen, Bin AU - Teng, Ying AU - Zhang, Xingguang AU - Lv, Xiaofeng AU - Yin, Yanling PY - 2016 DA - 2016/06/15 TI - Metformin Alleviated Aβ-Induced Apoptosis via the Suppression of JNK MAPK Signaling Pathway in Cultured Hippocampal Neurons SP - 1421430 VL - 2016 AB - 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. SN - 2314-6133 UR - https://doi.org/10.1155/2016/1421430 DO - 10.1155/2016/1421430 JF - BioMed Research International PB - Hindawi Publishing Corporation KW - ER -