Tau overexpression in transgenic mice induces glycogen synthase kinase 3β and β-catenin phosphorylation

Abstract The abnormal phosphorylations of tau, GSK3β, and β-catenin have been shown to perform a crucial function in the neuropathology of Alzheimer’s disease (AD). The primary objective of the current study was to determine the manner in which overexpressed htau23 interacts and regulates the behavi...

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Veröffentlicht in:Neuroscience 2007-05, Vol.146 (2), p.730-740
Hauptverfasser: Shim, S.B, Lim, H.J, Chae, K.R, Kim, C.K, Hwang, D.Y, Jee, S.W, Lee, S.H, Sin, J.S, Leem, Y.H, Cho, J.S, Lee, H.H, Choi, S.Y, Kim, Y.K
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Sprache:eng
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Zusammenfassung:Abstract The abnormal phosphorylations of tau, GSK3β, and β-catenin have been shown to perform a crucial function in the neuropathology of Alzheimer’s disease (AD). The primary objective of the current study was to determine the manner in which overexpressed htau23 interacts and regulates the behavior and phosphorylation characteristics of tau, GSK3β, and β-catenin. In order to accomplish this, transgenic mice expressing neuron-specific enolase ( NSE )-controlled human wild-type tau ( NSE/htau23 ) were created. Transgenic mice evidenced the following: (i) tendency toward memory impairments at later stages, (ii) dramatic overexpression of the tau transgene, coupled with increased tau phosphorylation and paired helical filaments (PHFs), (iii) high levels of GSK3β phosphorylation with advanced age, resulting in increases in the phosphorylations of tau and β-catenin, (iv) an inhibitory effect of lithium on the phosphorylations of tau, GSK3β, and β-catenin, but not in the non-transgenic littermate group. Therefore, the overexpression of NSE/htau23 in the brains of transgenic mice induces abnormal phosphorylations of tau, GSK3β, and β-catenin, which are ultimately linked to neuronal degeneration in cases of AD. These transgenic mice are expected to prove useful for the development of new drugs for the treatment of AD.
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2007.01.041