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P2‐143: Estradiol attenuates tau hyperphosphorylation induced by upregulation of protein kinase‐A
Author(s) -
Zhu Ling-Qiang,
Liu Xin-An,
Wang Jian-Zhi
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.1216
Subject(s) - hyperphosphorylation , forskolin , phosphorylation , western blot , protein kinase a , kinase , tau protein , chemistry , transfection , microbiology and biotechnology , downregulation and upregulation , biology , medicine , biochemistry , in vitro , alzheimer's disease , gene , disease
Protein kinase A (PKA) plays a crucial role in tau hyperphosphorylation, an early event of Alzheimer disease (AD), and 17β-estradiol replacement in aging women forestalls the onset of AD. However, the role of estradiol in PKA-induced tau hyperphosphorylation is not known. Here, we investigated the effect of 17β-estradiol on cAMP/PKA activity and the PKA-induced tau hyperphosphorylation in HEK293 cells stably expressing tau441. We found that 17β-estradiol effectively attenuated forskolin-induced overactivation of PKA and elevation of cAMP, and thus prevented tau from hyperphosphorylation. These data provide the first evidence that 17β-estradiol can inhibit PKA overactivation and the PKA-induced tau hyperphosphorylation, implying a preventive role of 17β-estradiol in AD-like tau pathology.