Valproate reduces tau phosphorylation via cyclin-dependent kinase 5 and glycogen synthase kinase 3 signaling pathways.
Brain Res Bull
; 85(3-4): 194-200, 2011 May 30.
Article
em En
| MEDLINE
| ID: mdl-21435383
ABSTRACT
Valproate (VPA) is a widely used anticonvulsant and mood-stabilizing drug. Recent studies have shown that VPA could reduce amyloid-ß generation, and improve memory deficits in transgenic mouse models of Alzheimer's disease (AD). However, whether VPA affects tau phosphorylation and the underlying mechanism has not been established. Here, we showed that systemic treatment of APP and presenilin 1 double transgenic mice with VPA (50mg/kg, once a day for 12 weeks), significantly reduced the levels of tau phosphorylation at the sites of Thr205, Ser396 and Thr231. Meanwhile, VPA treatment markedly reduced the activities of cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase 3ß (GSK3ß), two protein kinases involved in abnormal hyperphosphorylation of tau. In an okadaic acid-induced tau hyperphosphorylation SH-SY5Y cell model, the anti-tau-phosphorylation effect of VPA was further confirmed, accompanied by a marked decrease in the activities of CDK5 and GSK3ß. Our present data suggest that the inhibitory effects of VPA on tau hyperphosphorylation might be mediated through both CDK5 and GSK3ß signaling pathways.
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Ácido Valproico
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Proteínas tau
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Quinase 3 da Glicogênio Sintase
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Inibidores Enzimáticos
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Quinase 5 Dependente de Ciclina
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article