Alzheimer's disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules
Alzheimer's disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules
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DOI：
10.1038/nm0796-783
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发表时间：
1996-07-01
期刊：
影响因子：
82.9
通讯作者：
Iqbal, K
中科院分区：
文献类型：
--
作者：
Alonso, AD;GrundkeIqbal, I;Iqbal, K
在阿尔茨海默病(AD)中，微管相关蛋白tau异常过度磷酸化，并在变性的神经元中以成对螺旋细丝的形式积累。我们现在发现，在溶液中，正常的tau与AD过度磷酸化的tau(AD P-tau)以不饱和的方式结合，形成直径3.3+/-0.7 nm的大缠结细丝。这些缠结不能单独在相同处理的正常tau或AD P-tau中检测到，它们由几微米长的细丝组成，并用tau抗体标记。用碱性磷酸酶去磷酸化可以消除AD P-tau与正常tau聚集的能力，并防止形成缠结。AD P-tau分解由正常tau和微管蛋白组装而成的微管。这些数据为揭示tau蛋白的过度磷酸化如何导致AD时神经原纤维缠结的形成和受影响神经元的变性提供了线索。
Microtubule-associated protein tau becomes abnormally hyperphosphorylated in Alzheimer's disease (AD) and accumulates as tangles of paired helical filaments in neurons undergoing degeneration. We now show that in solution normal tau associates with the AD hyperphosphorylated tau (AD P-tau) in a nonsaturable fashion, forming large tangles of filaments 3.3 +/- 0.7 nm in diameter. These tangles, which are not detected in identically treated normal tau or AD P-tau alone, are made up of filaments several microns in length and are labeled with tau antibodies. Dephosphorylation with alkaline phosphatase abolishes the ability of AD P-tau to aggregate with normal tau and prevents tangle formation. AD P-tau disassembles microtubules assembled from normal tau and tubulin. These data provide insight into how the hyperphosphorylation of tau might lead to the formation of the neurofibrillary tangles and the degeneration of the affected neurons in AD.