Hong M, Zhukareva V, Vogelsberg-Ragaglia V, Wszolek Z, Reed L, Miller B I, Geschwind D H, Bird T D, McKeel D, Goate A, Morris J C, Wilhelmsen K C, Schellenberg G D, Trojanowski J Q, Lee V M
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Science. 1998 Dec 4;282(5395):1914-7. doi: 10.1126/science.282.5395.1914.
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.
在包括阿尔茨海默病、遗传性额颞叶痴呆以及与17号染色体相关的帕金森症（FTDP - 17）在内的多种神经退行性疾病中，tau蛋白会聚集形成细胞质内含物。在约20个FTDP - 17家族中已鉴定出tau基因的10多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，不同的致病突变会以不同方式改变大脑tau异构体的独特生化特性和化学计量。对具有不同FTDP - 17错义突变的重组tau蛋白进行的功能测定表明，除其中一个突变外，所有这些突变都通过降低tau与微管结合及促进微管组装的能力而参与疾病发病机制。
