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Published on: October 10, 2017
Conditional inactivation of Akt three isoforms causes tau hyperphosphorylation in the brain
Long Wang1, Shanshan Cheng1, Zhenyu Yin2
1Model Animal Research Center, MOE Key Laboratory of Model Animal for Disease Study, Nanjing University, 12 Xuefu Avenue, Nanjing, Jiangsu Province, 210061, China.
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.
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