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

Neuritic plaques in the brains are one of the pathological hallmarks of Alzheimer's disease (AD). Amyloid β-protein (Aβ), the central component of neuritic plaques, is derived from β-amyloid precursor protein (APP) after β- and γ-secretase cleavage. The molecular mechanism underlying the pathog...

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Autores principales: Qing, Hong, He, Guiqiong, Ly, Philip T. T., Fox, Christopher J., Staufenbiel, Matthias, Cai, Fang, Zhang, Zhuohua, Wei, Shengcai, Sun, Xiulian, Chen, Chia-Hsiung, Zhou, Weihui, Wang, Ke, Song, Weihong
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585842/
https://www.ncbi.nlm.nih.gov/pubmed/18955571
http://dx.doi.org/10.1084/jem.20081588
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author Qing, Hong
He, Guiqiong
Ly, Philip T. T.
Fox, Christopher J.
Staufenbiel, Matthias
Cai, Fang
Zhang, Zhuohua
Wei, Shengcai
Sun, Xiulian
Chen, Chia-Hsiung
Zhou, Weihui
Wang, Ke
Song, Weihong
author_facet Qing, Hong
He, Guiqiong
Ly, Philip T. T.
Fox, Christopher J.
Staufenbiel, Matthias
Cai, Fang
Zhang, Zhuohua
Wei, Shengcai
Sun, Xiulian
Chen, Chia-Hsiung
Zhou, Weihui
Wang, Ke
Song, Weihong
author_sort Qing, Hong
collection PubMed
description Neuritic plaques in the brains are one of the pathological hallmarks of Alzheimer's disease (AD). Amyloid β-protein (Aβ), the central component of neuritic plaques, is derived from β-amyloid precursor protein (APP) after β- and γ-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 Aβ production by inhibiting GSK-3β–mediated γ-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.
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spelling pubmed-25858422009-05-24 Valproic acid inhibits Aβ production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models Qing, Hong He, Guiqiong Ly, Philip T. T. Fox, Christopher J. Staufenbiel, Matthias Cai, Fang Zhang, Zhuohua Wei, Shengcai Sun, Xiulian Chen, Chia-Hsiung Zhou, Weihui Wang, Ke Song, Weihong J Exp Med Articles Neuritic plaques in the brains are one of the pathological hallmarks of Alzheimer's disease (AD). Amyloid β-protein (Aβ), the central component of neuritic plaques, is derived from β-amyloid precursor protein (APP) after β- and γ-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 Aβ production by inhibiting GSK-3β–mediated γ-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. The Rockefeller University Press 2008-11-24 /pmc/articles/PMC2585842/ /pubmed/18955571 http://dx.doi.org/10.1084/jem.20081588 Text en © 2008 Qing et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Articles
Qing, Hong
He, Guiqiong
Ly, Philip T. T.
Fox, Christopher J.
Staufenbiel, Matthias
Cai, Fang
Zhang, Zhuohua
Wei, Shengcai
Sun, Xiulian
Chen, Chia-Hsiung
Zhou, Weihui
Wang, Ke
Song, Weihong
Valproic acid inhibits Aβ production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models
title Valproic acid inhibits Aβ production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models
title_full Valproic acid inhibits Aβ production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models
title_fullStr Valproic acid inhibits Aβ production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models
title_full_unstemmed Valproic acid inhibits Aβ production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models
title_short Valproic acid inhibits Aβ production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models
title_sort valproic acid inhibits aβ production, neuritic plaque formation, and behavioral deficits in alzheimer's disease mouse models
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585842/
https://www.ncbi.nlm.nih.gov/pubmed/18955571
http://dx.doi.org/10.1084/jem.20081588
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