Mutation-specific functional impairments in distinct Tau isoforms of hereditary FTDP-17
Mutation-specific functional impairments in distinct Tau isoforms of hereditary FTDP-17
复制标题
DOI：
10.1126/science.282.5395.1914
复制
发表时间：
1998-12-04
期刊：
影响因子：
56.9
通讯作者：
Lee, VMY
中科院分区：
文献类型：
--
作者：
Hong, M;Zhukareva, V;Lee, VMY
Tau 蛋白在许多神经退行性疾病中聚集为细胞质内含物，包括阿尔茨海默病、遗传性额颞叶痴呆和 17 号染色体相关帕金森病 (FTDP-17)。已在大约 20 个 FTDP-17 家族中鉴定出 tau 基因中超过 10 个外显子和内含子突变。对 FTDP-17 患者大脑中可溶性和不溶性 tau 蛋白的分析表明，不同的致病性突变差异性地改变了脑 tau 亚型的不同生化特性和化学计量，具有不同 FTDP-17 错义突变的重组 tau 蛋白的功能分析表明，除其中一种突变外，所有这些突变都通过降低 tau 结合能力而与疾病发病机制有关。 微管并促进微管组装。
Tau proteins aggregate as cytoplasmic inclusions in a number of neurodegenerative diseases, including Alzheimer's disease and hereditary frontotemporal dementia and parkinsonism Linked to chromosome 17 (FTDP-17). Over 10 exonic and intronic mutations in the tau gene have been identified in about 20 FTDP-17 families. Analyses of soluble and insoluble tau proteins from brains of FTDP-17 patients indicated that different pathogenic mutations differentially altered distinct biochemical properties and stoichiometry of brain tau isoforms, Functional assays of recombinant tau proteins with different FTDP-17 missense mutations implicated all but one of these mutations in disease pathogenesis by reducing the ability of tau to bind microtubules and promote microtubule assembly.