Estradiol attenuates tau hyperphosphorylation induced by upregulation of protein kinase-A.

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.

journal_name

Neurochem Res

journal_title

Neurochemical research

authors

Liu XA,Zhu LQ,Zhang Q,Shi HR,Wang SH,Wang Q,Wang JZ

doi

10.1007/s11064-008-9638-4

subject

Has Abstract

pub_date

2008-09-01 00:00:00

pages

1811-20

issue

9

eissn

0364-3190

issn

1573-6903

journal_volume

33

pub_type

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