Biochemical classification of tauopathies by immunoblot, protein sequence and mass spectrometric analyses of sarkosyl-insoluble and trypsin-resistant tau.
Biochemical classification of tauopathies by immunoblot, protein sequence and mass spectrometric analyses of sarkosyl-insoluble and trypsin-resistant tau.
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DOI：
10.1007/s00401-015-1503-3
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发表时间：
2016-02
影响因子：
12.7
通讯作者：
Hasegawa M
中科院分区：
文献类型：
--
作者：
Taniguchi-Watanabe S;Arai T;Kametani F;Nonaka T;Masuda-Suzukake M;Tarutani A;Murayama S;Saito Y;Arima K;Yoshida M;Akiyama H;Robinson A;Mann DMA;Iwatsubo T;Hasegawa M
细胞内丝状tau病理是tau蛋白病的定义特征，其形成神经退行性疾病的子集。我们已经分析了阿尔茨海默病中的病理性tau蛋白，以及与tau蛋白病相关的额颞叶变性，包括皮克体、皮质基底节变性、进行性核上性麻痹和MAPT内含子突变的病例。我们发现，病理性tau蛋白种类的C-末端带型对于每种疾病是不同的。胰蛋白酶抗性tau蛋白的免疫印迹分析表明，这些疾病中7-18 kDa片段的不同带型可能反映了tau蛋白分子种类的不同构象。蛋白质序列和质谱分析显示，tau蛋白的羧基末端区域（残基243-406）包含tau蛋白聚集体的蛋白酶抗性核心单元，并且所涉及的序列长度和精确区域在疾病中不同。这些独特组装的tau核心可用于分类和诊断疾病菌株。基于这些结果，我们提出了一个新的临床病理分类的基础上的生化特性的tau蛋白病。本文的在线版本（doi：10.1007/s 00401 -015-1503-3）包含补充材料，可供授权用户使用。
Intracellular filamentous tau pathology is the defining feature of tauopathies, which form a subset of neurodegenerative diseases. We have analyzed pathological tau in Alzheimer’s disease, and in frontotemporal lobar degeneration associated with tauopathy to include cases with Pick bodies, corticobasal degeneration, progressive supranuclear palsy, and ones due to intronic mutations in MAPT. We found that the C-terminal band pattern of the pathological tau species is distinct for each disease. Immunoblot analysis of trypsin-resistant tau indicated that the different band patterns of the 7–18 kDa fragments in these diseases likely reflect different conformations of tau molecular species. Protein sequence and mass spectrometric analyses revealed the carboxyl-terminal region (residues 243–406) of tau comprises the protease-resistant core units of the tau aggregates, and the sequence lengths and precise regions involved are different among the diseases. These unique assembled tau cores may be used to classify and diagnose disease strains. Based on these results, we propose a new clinicopathological classification of tauopathies based on the biochemical properties of tau. The online version of this article (doi:10.1007/s00401-015-1503-3) contains supplementary material, which is available to authorized users.