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Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2015

Open Access 01-12-2015 | Short report

Conditional inactivation of Akt three isoforms causes tau hyperphosphorylation in the brain

Authors: Long Wang, Shanshan Cheng, Zhenyu Yin, Congyu Xu, Shuangshuang Lu, Jinxing Hou, Tingting Yu, Xiaolei Zhu, Xiaoyan Zou, Ying Peng, Yun Xu, Zhongzhou Yang, Guiquan Chen

Published in: Molecular Neurodegeneration | Issue 1/2015

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Abstract

Background

Tau hyperphosphorylation plays a critical role in neurodegenerative diseases [EMBO Mol Med. 6:1142-60, 2014; Annu Rev Neurosci. 24:1121-59, 2001]. Recent evidence has shown that Akt is down-regulated in AD [J Pathol. 225:54-62, 2011]. However, it remained unknown which pathological process, e.g. tau pathology or neuron death, Akt may contribute to. In this study, Cre-loxP technique was employed to generate a viable Akt three isoforms conditional knockout (Akt cTKO) mouse in which total Akt levels were dramatically reduced in the adult brain.

Results

Significantly increased levels of tau phosphorylated (p-tau) at various sites were observed in Akt cTKO mice as compared to age-matched littermate controls. Increased levels for phosphorylated GSK3α and phosphorylated PKA substrates were detected in Akt cTKO brains. In contrast, no significant changes on p-tau levels were found in Akt1 −/−, Akt2 −/− or Akt3 −/− mice.

Conclusions

Akt may regulate tau phosphorylation in the adult brain by affecting activities for PKA and GSK3α.
Appendix
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Metadata
Title
Conditional inactivation of Akt three isoforms causes tau hyperphosphorylation in the brain
Authors
Long Wang
Shanshan Cheng
Zhenyu Yin
Congyu Xu
Shuangshuang Lu
Jinxing Hou
Tingting Yu
Xiaolei Zhu
Xiaoyan Zou
Ying Peng
Yun Xu
Zhongzhou Yang
Guiquan Chen
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2015
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/s13024-015-0030-y

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