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

Xin An Liu; Ling Qiang Zhu; Qi Zhang; Hai Rong Shi; Shao Hui Wang; Qun Wang; Jian Zhi Wang

doi:10.1007/s11064-008-9638-4

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

Xin An Liu
, Ling Qiang Zhu
, Qi Zhang
, Hai Rong Shi
, Shao Hui Wang
, Qun Wang
, Jian Zhi Wang

Research output: Contribution to journal › Article › peer-review

55 Scopus citations

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.

Original language	English
Pages (from-to)	1811-1820
Number of pages	10
Journal	Neurochemical Research
Volume	33
Issue number	9
DOIs	https://doi.org/10.1007/s11064-008-9638-4
State	Published - Sep 2008
Externally published	Yes

Keywords

Alzheimer's disease
Estradiol
Protein kinase A
Tau phosphorylation

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10.1007/s11064-008-9638-4

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title = "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 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.",

keywords = "Alzheimer's disease, Estradiol, Protein kinase A, Tau phosphorylation",

author = "Liu, \{Xin An\} and Zhu, \{Ling Qiang\} and Qi Zhang and Shi, \{Hai Rong\} and Wang, \{Shao Hui\} and Qun Wang and Wang, \{Jian Zhi\}",

year = "2008",

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doi = "10.1007/s11064-008-9638-4",

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T1 - Estradiol attenuates tau hyperphosphorylation induced by upregulation of protein kinase-A

AU - Liu, Xin An

AU - Zhu, Ling Qiang

AU - Zhang, Qi

AU - Shi, Hai Rong

AU - Wang, Shao Hui

AU - Wang, Qun

AU - Wang, Jian Zhi

PY - 2008/9

Y1 - 2008/9

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Estradiol

KW - Protein kinase A

KW - Tau phosphorylation

UR - https://www.scopus.com/pages/publications/48349124965

U2 - 10.1007/s11064-008-9638-4

DO - 10.1007/s11064-008-9638-4

M3 - Article

C2 - 18338250

AN - SCOPUS:48349124965

SN - 0364-3190

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SP - 1811

EP - 1820

JO - Neurochemical Research

JF - Neurochemical Research

IS - 9

ER -

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

Abstract

Keywords

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