Wang Jian-Zhi, Wang Zhi-Hao, Tian Qing
Department of Pathology and Pathophysiology, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China,
Neurosci Bull. 2014 Apr;30(2):359-66. doi: 10.1007/s12264-013-1415-y. Epub 2014 Mar 14.
Since abnormal post-translational modifications or gene mutations of tau have been detected in over twenty neurodegenerative disorders, tau has attracted widespread interest as a target protein. Among its various post-translational modifications, phosphorylation is the most extensively studied. It is recognized that tau hyperphosphorylation is the root cause of neurodegeneration in Alzheimer's disease (AD); however, it is not clear how it causes neurodegeneration. Based on the findings that tau hyperphosphorylation leads to the escape of neurons from acute apoptosis and simultaneously impairs the function of neurons, we have proposed that the nature of AD neurodegeneration is the consequence of aborted apoptosis induced by tau phosphorylation. Therefore, proper manipulation of tau hyperphosphorylation could be promising for arresting AD neurodegeneration. In this review, the neuroprotective and neurodegenerative effects of tau hyperphosphorylation and our thoughts regarding their relationship are presented.
由于在二十多种神经退行性疾病中均检测到tau蛋白存在异常的翻译后修饰或基因突变，tau蛋白作为一种靶蛋白已引起广泛关注。在其各种翻译后修饰中，磷酸化是研究最为广泛的。人们认识到，tau蛋白过度磷酸化是阿尔茨海默病（AD）神经退行性变的根本原因；然而，目前尚不清楚它是如何导致神经退行性变的。基于tau蛋白过度磷酸化导致神经元逃脱急性凋亡并同时损害神经元功能这一发现，我们提出AD神经退行性变的本质是由tau蛋白磷酸化诱导的凋亡中止的结果。因此，适当调控tau蛋白过度磷酸化有望阻止AD神经退行性变。在这篇综述中，我们阐述了tau蛋白过度磷酸化的神经保护和神经退行性变作用以及我们对它们之间关系的看法。
