GSK-3 dependent phosphoepitopes recognized by PHF-1 and AT-8 antibodies are present in different tau isoforms
GSK-3 dependent phosphoepitopes recognized by PHF-1 and AT-8 antibodies are present in different tau isoforms
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DOI：
10.1016/j.neurobiolaging.2003.04.002
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发表时间：
2003-12-01
影响因子：
4.2
通讯作者：
Avila, J
中科院分区：
文献类型：
--
作者：
Hernández, F;Lucas, JJ;Avila, J
众所周知，形成像阿尔茨海默病(AD)这样的肌萎缩侧索硬化症(AD)的聚集体的tau蛋白被过度磷酸化。在AD中，许多过度磷酸化的部位也可以在非病理对照的大脑中发现，尽管程度较小。在这些位点上能够磷酸化tau的不同的激酶中，GSK-3已经成为AD发病机制中的关键效应者，因为它与许多参与AD遗传学的蛋白质相互作用。在这项工作中，我们测试了对照样品是否只显示出磷酸化的tau分子的数量减少，或者如果不同位置的磷酸化以不同的tau亚型发生，而在病理情况下，单个tau亚型在不同的位置同时被修饰。我们的结果表明，第二种可能性存在，不同tau亚型的磷酸化差异可能是由于这些不同tau亚型在神经元中的不同亚细胞分布所致。(C)2003年，爱思唯尔公司出版。
It is widely known that the tau protein that forms the aggregates found in tauopathies like Alzheimer's disease (AD) is hyperphosphorylated. Many of the sites that are hyperphosphorylated in AD can also be found phosphorylated in non-pathological control brains, although to a lesser extend. Among the different kinases that are able to phosphorylate tau in these sites, GSK-3 has emerged as a key effector of AD pathogenesis in view of its interaction with many of the proteins involved in the ethiology of AD. In this work, we have tested if control samples show only a decrease in the amount of phosphorylated tau molecules, or if the phosphorylation at different sites occurs in different tau isoforms, whereas in the pathological situation a single tau isoform is modified simultaneously at the different sites. Our results indicate that the second possibility takes place and that the differences in the phosphorylation of different tau isoforms could be due to a different subcellular distribution of these different tau isoforms in a neuron. (C) 2003 Published by Elsevier Inc.