Goedert M, Jakes R, Crowther R A
Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
FEBS Lett. 1999 May 7;450(3):306-11. doi: 10.1016/s0014-5793(99)00508-6.
Missense mutations and intronic mutations in the gene for microtubule-associated protein tau cause frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). Most missense mutations have as likely primary effect a reduced ability of tau to interact with microtubules. We report here an additional effect of several missense mutations, namely the stimulation of heparin-induced filament assembly of recombinant tau, despite the absence of any change in structure indicated by circular dichroism. These findings indicate that missense mutations in tau lead to frontotemporal dementia through potentially multiple mechanisms.
微管相关蛋白tau基因中的错义突变和内含子突变会导致与17号染色体相关的额颞叶痴呆和帕金森综合征（FTDP - 17）。大多数错义突变可能主要影响tau与微管相互作用的能力。我们在此报告了几个错义突变的另一个效应，即尽管圆二色性显示结构没有任何变化，但它们能刺激重组tau的肝素诱导丝状组装。这些发现表明，tau基因中的错义突变可能通过多种机制导致额颞叶痴呆。
