Valproic acid inhibits Aβ production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models

Abstract

Neuritic plaques in the brains are one of the pathological hallmarks of Alzheimer's disease (AD). Amyloid beta-protein (Abeta), the central component of neuritic plaques, is derived from beta-amyloid precursor protein (APP) after beta- and gamma-secretase cleavage. The molecular mechanism underlying the pathogenesis of AD is not yet well defined, and there has been no effective treatment for AD. Valproic acid (VPA) is one of the most widely used anticonvulsant and mood-stabilizing agents for treating epilepsy and bipolar disorder. We found that VPA decreased Abeta production by inhibiting GSK-3beta-mediated gamma-secretase cleavage of APP both in vitro and in vivo. VPA treatment significantly reduced neuritic plaque formation and improved memory deficits in transgenic AD model mice. We also found that early application of VPA was important for alleviating memory deficits of AD model mice. Our study suggests that VPA may be beneficial in the prevention and treatment of AD.

DOI: 10.1084/jem.20081588

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@article{Qing2008ValproicAI, title={Valproic acid inhibits Aβ production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models}, author={Hong Hong Qing and G. P. He and Philip T. T. Ly and Christopher J. Fox and Matthias Staufenbiel and Fang Cai and Zhuohua Zhang and Shengcai Wei and Xiulian Sun and Chia-Hsiung Chen and Weihui Zhou and Ke Wang and Weihong Song}, journal={The Journal of Experimental Medicine}, year={2008}, volume={205}, pages={2781 - 2789} }