CLONING AND SEQUENCING OF THE CDNA-ENCODING A CORE PROTEIN OF THE PAIRED HELICAL FILAMENT OF ALZHEIMER-DISEASE - IDENTIFICATION AS THE MICROTUBULE-ASSOCIATED PROTEIN TAU
CLONING AND SEQUENCING OF THE CDNA-ENCODING A CORE PROTEIN OF THE PAIRED HELICAL FILAMENT OF ALZHEIMER-DISEASE - IDENTIFICATION AS THE MICROTUBULE-ASSOCIATED PROTEIN TAU
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DOI：
10.1073/pnas.85.11.4051
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发表时间：
1988-06-01
影响因子：
11.1
通讯作者：
KLUG, A
中科院分区：
文献类型：
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作者：
GOEDERT, M;WISCHIK, CM;KLUG, A
筛选从阿尔茨海默病患者额叶皮层和胎儿人脑制备的cDNA文库，分离出阿尔茨海默病成对螺旋丝的核心蛋白cDNA。利用该核心蛋白的部分氨基酸序列设计合成寡核苷酸探针。cDNA编码一种由352个氨基酸组成的蛋白质，在其羧基末端的一半中包含一个特征氨基酸重复序列。该蛋白与小鼠微管相关蛋白tau的序列高度同源，因此构成了小鼠tau的人类等效物。RNA印迹分析显示存在两种主要转录本，长度分别为6和2千碱基，在正常人脑中分布广泛。在阿尔茨海默病患者的额叶皮层中发现了正常数量的Tau蛋白mrna。证明至少部分tau蛋白形成成对螺旋细丝核心的一个组成部分，为理解成对螺旋细丝的形成模式开辟了道路，从而最终了解阿尔茨海默病的发病机制。
Screening of cDNA libraries prepared from the frontal cortex of an Alzheimer disease patient and from fetal human brain has led to isolation of the cDNA for a core protein of the paired helical filament of Alzheimer disease. The partial amino acid sequence of this core protein was used to design synthetic oligonucleotide probes. The cDNA encodes a protein of 352 amino acids that contains a characteristic amino acid repeat in its carboxyl-terminal half. This protein is highly homologous to the sequence of the mouse microtubule-associated protein tau and thus constitutes the human equivalent of mouse tau. RNA blot analysis indicates the presence of two major transcripts, 6 and 2 kilobases long, with a wide distribution in normal human brain. Tau protein mRNAs were found in normal amounts in the frontal cortex from patients with Alzheimer disease. The proof that at least part of tau protein forms a component of the paired helical filament core opens the way to understanding the mode of formation of paired helical filaments and thus, ultimately, the pathogenesis of Alzheimer disease.