摘要
背景：各种神经退行性疾病，包括阿尔茨海默病（AD），与脑损伤中异常的过度磷酸化微管相关蛋白tau积聚有关。最近的研究集中于由另一种翻译后修饰（PTM）引起的毒性，即tau蛋白的赖氨酸（K）残基的乙酰化。因为有许多乙酰化位点，一些研究引入了使用从赖氨酸到谷氨酰胺（Q）的氨基酸取代的tau乙酰化的模拟物。然而，人类tau蛋白含有20多个乙酰化位点;因此，研究乙酰化tau的影响是困难的。 目的：本文，作者在计算机上使用SIFT，PolyPhen-2和PROVEAN评估乙酰化效应，其可以基于tau同种型中的序列同源性或蛋白质结构来估计氨基酸取代的影响。此外，他们还研究了使用华尔兹对tau蛋白淀粉样蛋白形成的27种乙酰化作用。 结果：15种乙酰化模拟物估计是最有害的，这表明在人类tau蛋白中可能存在新的致病性乙酰化位点。有趣的是，根据同种型的类型，乙酰化模拟物的有害作用是不同的。此外，预测所有乙酰化模拟物是人tau蛋白的密码子274-279处淀粉样蛋白形成的区域。值得注意的是，密码子311（K311Q）的乙酰化模拟诱导了位于人tau蛋白的密码子306-311上的另外的淀粉样蛋白区域的形成。 结论：据我们所知，这是第一次同时对27种人类tau蛋白残基的乙酰化状态进行计算机内评估。
关键词: 计算机分析，tau，阿尔茨海默病，乙酰化，模拟，神经退行性疾病。
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