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Published on: October 10, 2017
Estradiol attenuates tau hyperphosphorylation induced by upregulation of protein kinase-A
Xin-An Liu1, Ling-Qiang Zhu, Qi Zhang
1Pathophysiology Department, Tongji Medical College, Hua-Zhong University of Science and Technology, Wuhan, 430030, PR China.
Abstract:
Protein kinase A (PKA) plays a crucial role in tau hyperphosphorylation, an early event of Alzheimer disease (AD), and 17beta-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 17beta-estradiol on cAMP/PKA activity and the PKA-induced tau hyperphosphorylation in HEK293 cells stably expressing tau441. We found that 17beta-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 17beta-estradiol can inhibit PKA overactivation and the PKA-induced tau hyperphosphorylation, implying a preventive role of 17beta-estradiol in AD-like tau pathology.
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