Neurochemical Research

, Volume 33, Issue 9, pp 1811–1820

Estradiol Attenuates Tau Hyperphosphorylation Induced by Upregulation of Protein Kinase-A

Original Paper

DOI: 10.1007/s11064-008-9638-4

Cite this article as:
Liu, XA., Zhu, LQ., Zhang, Q. et al. Neurochem Res (2008) 33: 1811. doi:10.1007/s11064-008-9638-4

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 diseaseTau phosphorylationEstradiolProtein kinase A

Abbreviations

AD

Alzheimer’s disease

NFT

Neurofibrillary tangle

HEK293

Human embryonic kidney cell

CCK-8

Cell counting kit-8

BCA

Bicinchoninic acid

PKA

Protein kinase A

PKAcα

PKA catalytic subunit α

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Pathophysiology Department, Tongji Medical CollegeHua-Zhong University of Science and TechnologyWuhanP.R. China
  2. 2.Key Laboratory of Neurological Diseases of the Education Ministry and Hubei Province, Tongji Medical CollegeHua-Zhong University of Science and TechnologyWuhanP.R. China