Valproic acid inhibits Abeta production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models.
Valproic acid inhibits Abeta production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models.
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DOI：
10.1084/jem.20081588
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发表时间：
2008-11-24
期刊：
影响因子：
--
通讯作者：
Song W
中科院分区：
文献类型：
--
作者：
Qing H;He G;Ly PT;Fox CJ;Staufenbiel M;Cai F;Zhang Z;Wei S;Sun X;Chen CH;Zhou W;Wang K;Song W
脑内神经炎性斑块是阿尔茨海默病（AD）的病理标志之一。β-淀粉样蛋白（Aβ）是神经炎斑的主要成分，是由β-淀粉样前体蛋白（APP）经β-和γ-分泌酶裂解而成。AD发病机制的分子机制尚未完全明确，也没有有效的治疗方法。丙戊酸（VPA）是治疗癫痫和双相情感障碍最广泛使用的抗惊厥和情绪稳定剂之一。我们发现，VPA通过抑制GSK-3β介导的γ-分泌酶对APP的切割，在体外和体内减少Aβ的产生。VPA治疗显著减少了转基因AD模型小鼠的神经炎斑块形成并改善了记忆缺陷。早期应用VPA对改善AD模型小鼠的记忆障碍有重要作用。我们的研究表明，丙戊酸钠可能是有益的预防和治疗AD。
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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影响因子：
4.8
作者：
Ikeuchi, T;Sisodia, SS
通讯作者：
Sisodia, SS
DOI：
10.1016/s0006-291x(84)80190-4
发表时间：
1984-01-01
影响因子：
3.1
作者：
GLENNER, GG;WONG, CW
通讯作者：
WONG, CW
影响因子：
64.8
作者：
Phiel, CJ;Wilson, CA;Klein, PS
通讯作者：
Klein, PS
影响因子：
56.9
作者：
LEVYLAHAD, E;WASCO, W;TANZI, RE
通讯作者：
TANZI, RE
影响因子：
4
作者：
Kim, AJ;Shi, YY;Werstuck, GH
通讯作者：
Werstuck, GH