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BioMed Research International
Volume 2016, Article ID 1421430, 8 pages
http://dx.doi.org/10.1155/2016/1421430
Research Article

Metformin Alleviated Aβ-Induced Apoptosis via the Suppression of JNK MAPK Signaling Pathway in Cultured Hippocampal Neurons

1Department of Endocrinology and Metabolism, General Hospital of Beijing Military Region, Beijing 100700, China
2Affiliated Hospital of Beijing Institute of Aeronautical Material, Beijing 100060, China
3Department of Neurobiology and Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China

Received 14 March 2016; Revised 21 May 2016; Accepted 25 May 2016

Academic Editor: Amit K. Srivastava

Copyright © 2016 Bin Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.