Details

Autor(en) / Beteiligte

• Shi, Hai-rong
• Zhu, Ling-qiang
• Wang, Shao-hui
• Liu, Xin-an
• Tian, Qing
• Zhang, Qi
• Wang, Qun
• Wang, Jian-zhi

Titel

17[beta]-estradiol attenuates glycogen synthase kinase-3[beta] activation and tau hyperphosphorylation in Akt-independent manner

Ist Teil von

• Journal of neural transmission, 2008-06, Vol.115 (6), p.879

Ort / Verlag

Wien: Springer Nature B.V

Erscheinungsjahr

2008

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Decline of estrogen is associated with high incidence of Alzheimer's disease (AD) characterized pathologically with tau hyperphosphorylation, and glycogen synthase kinase-3β (GSK-3β) is a major tau kinase. However, the role of estrogen on GSK3β-induced tau hyperphosphorylation is elusive. Here, we treated N2a cells with wortmannin (Wort) and GF-109203X (GFX) or gene transfection to activate GSK-3β and to induce tau hyperphosphorylation and then the effects of 17β-estradiol (βE2) on tau phosphorylation and GSK-3β activity were studied. We found that βE2 could attenuate tau hyperphosphorylation at multiple AD-related sites, including Ser396/404, Thr231, Thr205, and Ser199/202, induced by Wort/GFX or transient overexpression of GSK-3β. Simultaneously, it increased the level of Ser9-phosphorylated (inactive) GSK-3β. To study whether the protective effect of βE2 on GSK-3β and tau phosphorylation involves protein kinase B (Akt), an upstream effector of GSK-3, we transiently expressed the dominant negative Akt (dnAkt) in the cells. We found that βE2 could attenuate Wort/GFX-induced GSK-3β activation and tau hyperphosphorylation with Akt-independent manner. It suggests that βE2 may arrest AD-like tau hyperphosphorylation by directly targeting GSK-3β. [PUBLICATION ABSTRACT]