随着β淀粉样蛋白（Aβ）过量产生，p70激酶激活和tau蛋白磷酸化（S262）平行增加。

Parallel increase in p70 kinase activation and tau phosphorylation (S262) with Abeta overproduction.

作者信息

Zhou Xin-Wen, Tanila Heikki, Pei Jin-Jing

机构信息

Karolinska Institutet, Department of Neurobiology, Care Sciences and Society (NVS), KI--Alzheimer's Disease Research Center, Geriatrics lab, Novum, Huddinge, Sweden.

出版信息

FEBS Lett. 2008 Jan 23;582(2):159-64. doi: 10.1016/j.febslet.2007.11.078. Epub 2007 Dec 7.

DOI:10.1016/j.febslet.2007.11.078

PMID:18068129

Abstract

This study set out to search for a link between overproduction of Abeta and p70S6 kinase (p70S6K) phosphorylation/activation. Results showed that levels of p-p70S6K at T421/S424 and T389 are significantly increased in mouse N2a neuroblastoma cells carrying human APP with Swedish mutation (APPswe), and in transgenic APPswe/PS1 (A246E) mice as compared with respective controls, corresponding to the increase of tau phosphorylation at S262. This parallel increase in p70S6K activation and tau phosphorylation could be demonstrated by treating wild-type N2a cells with Abeta25-35. Our results suggest that the Abeta deposition in senile plaques in Alzheimer disease brains might be a primary event that activates p70S6K and phosphorylates tau at S262, resulting in microtubule disruption.

摘要

本研究旨在探寻β淀粉样蛋白（Aβ）过量产生与p70核糖体蛋白S6激酶（p70S6K）磷酸化/激活之间的联系。结果显示，与各自的对照组相比，携带瑞典突变型人淀粉样前体蛋白（APPswe）的小鼠N2a神经母细胞瘤细胞以及转基因APPswe/早老素1（PS1，A246E）小鼠中，苏氨酸421/丝氨酸424和苏氨酸389位点的磷酸化p70S6K水平显著升高，这与丝氨酸262位点tau蛋白磷酸化的增加相对应。用Aβ25-35处理野生型N2a细胞可证明p70S6K激活和tau蛋白磷酸化的这种平行增加。我们的结果表明，阿尔茨海默病大脑中淀粉样斑块中的Aβ沉积可能是激活p70S6K并使丝氨酸262位点的tau蛋白磷酸化，从而导致微管破坏的主要事件。