Neighbored phosphorylation sites as PHF-tau specific markers in Alzheimer's disease.
Neighbored phosphorylation sites as PHF-tau specific markers in Alzheimer's disease.
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邻近磷酸化位点作为阿尔茨海默病中 PHF-tau 特异性标记。
DOI：
10.1016/j.bbrc.2006.05.201
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发表时间：
2006
影响因子：
3.1
通讯作者：
R. Hoffmann
中科院分区：
文献类型：
--
作者：
D. Singer;J. Lehmann;Katja Hanisch;W. Härtig;R. Hoffmann
神经元缠结是阿尔茨海默病（AD）的主要病理标志，是过度磷酸化的微管相关tau蛋白（PHF-tau）的沉积。然而，磷酸化模式与AD的病因或进展之间的联系仍然缺失。本文报道的工作集中在PHF-tau特异性的局部磷酸化模式，在Thr 212/Ser 214和Thr 231/Ser 235使用单克隆抗体（mAb）产生相应的修饰肽。所获得的6个单克隆抗体的结合基序的特征在于与非，单，双磷酸化肽以及末端缩短的序列。五个单克隆抗体染色神经纤维缠结，神经炎斑块，和神经纤维丝从AD病例的尸检大脑。在ELISA和Western印迹分析中，四种mAb识别PHF-tau而对正常人tau、牛tau和去磷酸化PHF-tau没有显著的交叉反应性。因此，双磷酸化足以区分PHF-tau与所有其他tau版本，并且不需要假定该区域的任何PHF-tau特异性构象。
Neurofibrillary tangles, which represent a major pathological hallmark in Alzheimer’s disease (AD), are deposits of the hyperphosphorylated microtubule-associated tau protein (PHF-tau). However, a link between the phosphorylation pattern and the cause or the progress of AD is still missing. The work reported here focused on PHF-tau specific local phosphorylation patterns at Thr212/Ser214 and Thr231/Ser235 using monoclonal antibodies (mAb) generated against correspondingly modified peptides. The binding motifs of the obtained six mAbs were characterized with non-, mono-, and double-phosphorylated peptides as well as terminally shortened sequences. Five mAbs stained neurofibrillary tangles, neuritic plaques, and neuropil threads from autoptic brains of AD cases. Four mAbs recognized PHF-tau without significant cross-reactivity towards normal human tau, bovine tau, and dephosphorylated PHF-tau in ELISA and Western blot analysis. Thus, double phosphorylation is sufficient to distinguish PHF-tau from all other tau versions and there is no need to postulate any PHF-tau specific conformation for this region.
DOI：
10.1016/0006-291x(89)91150-9
发表时间：
1989-09-29
影响因子：
3.1
作者：
JOHNSON, GVW;JOPE, RS;BINDER, LI
通讯作者：
BINDER, LI