Estradiol Attenuates Tau Hyperphosphorylation Induced by Upregulation of Protein Kinase-A |
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Authors: | Xin-An Liu Ling-Qiang Zhu Qi Zhang Hai-Rong Shi Shao-Hui Wang Qun Wang Jian-Zhi Wang |
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Institution: | (1) Pathophysiology Department, Tongji Medical College, Hua-Zhong University of Science and Technology, Wuhan, 430030, P.R. China;(2) Key Laboratory of Neurological Diseases of the Education Ministry and Hubei Province, Tongji Medical College, Hua-Zhong University of Science and Technology, Wuhan, 430030, P.R. China |
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Abstract: | 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.
Xin-An Liu and Ling-Qiang Zhu contributed equally to this work. |
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Keywords: | Alzheimer’ s disease Tau phosphorylation Estradiol Protein kinase A |
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