Gong C-X, Liu F, Grundke-Iqbal I, Iqbal K
Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA.
J Neural Transm (Vienna). 2005 Jun;112(6):813-38. doi: 10.1007/s00702-004-0221-0. Epub 2004 Oct 27.
Microtubule-associated protein tau undergoes several post-translational modifications and aggregates into paired helical filaments (PHFs) in Alzheimer's disease (AD) and other tauopathies. These modifications of tau include hyperphosphorylation, glycosylation, ubiquitination, glycation, polyamination, nitration, and proteolysis. Hyperphosphorylation and glycosylation are crucial to the molecular pathogenesis of neurofibrillary degeneration of AD. The others appear to represent failed mechanisms for neurons to remove damaged, misfolded, and aggregated proteins. This review summarizes the abnormal post-translational modifications of tau and discusses the pathophysiological relevance of hyperphosphorylation and glycosylation of tau. Total tau and phosphorylated tau levels in cerebrospinal fluid as a diagnostic biomarkers are also reviewed. Analyses of the current advances in tau modifications suggest that intervention addressing these abnormalities may offer promising therapeutic opportunities to prevent and treat neurofibrillary degeneration of AD and other tauopathies.
微管相关蛋白tau会经历多种翻译后修饰，并在阿尔茨海默病（AD）和其他tau蛋白病中聚集成双螺旋丝（PHF）。tau蛋白的这些修饰包括过度磷酸化、糖基化、泛素化、糖基化终产物修饰、多胺化、硝化和蛋白水解。过度磷酸化和糖基化对AD神经原纤维变性的分子发病机制至关重要。其他修饰似乎代表了神经元清除受损、错误折叠和聚集蛋白的失效机制。本综述总结了tau蛋白异常的翻译后修饰，并讨论了tau蛋白过度磷酸化和糖基化的病理生理相关性。还综述了脑脊液中总tau蛋白和磷酸化tau蛋白水平作为诊断生物标志物的情况。对tau蛋白修饰当前进展的分析表明，针对这些异常的干预可能为预防和治疗AD及其他tau蛋白病的神经原纤维变性提供有前景的治疗机会。
