Alonso Alejandra del C, Li Ben, Grundke-Iqbal Inge, Iqbal Khalid
Department of Biology and Center for Developmental Neuroscience and Developmental Disabilities, College of Staten Island, The City University of New York, Staten Island, NY 10314, USA.
Curr Alzheimer Res. 2008 Aug;5(4):375-84. doi: 10.2174/156720508785132307.
The accumulation of hyperphosphorylated tau is a common feature of several dementias. Tau is one of the brain microtubule-associated proteins. Here we discuss tau's function in microtubule assembly and stabilization and with regards to tau's interactions with other proteins, membranes, and DNA. We describe and analyze important posttranslational modifications: hyperphosphorylation, glycosylation, ubiquitination, glycation, polyamination, nitration, and truncation. We discuss how these post-translational modifications can alter tau's biological function and what is known about tau self-assembly, and we propose a mechanism of tau polymerization. We analyze the impact of natural mutations on tau that cause fronto-temporal dementia associated with chromosome 17 (FTDP-1 7). Finally, we consider whether tau accumulation or its conformational change is related to tau-induced neurodegeneration, and we propose a mechanism of neurodegeneration.
高度磷酸化tau蛋白的积累是几种痴呆症的共同特征。Tau蛋白是大脑中与微管相关的蛋白之一。在此，我们讨论tau蛋白在微管组装和稳定中的作用，以及tau蛋白与其他蛋白质、膜和DNA的相互作用。我们描述并分析重要的翻译后修饰：高度磷酸化、糖基化、泛素化、糖化、多胺化、硝化和截短。我们讨论这些翻译后修饰如何改变tau蛋白的生物学功能以及关于tau蛋白自我组装的已知情况，并提出tau蛋白聚合的机制。我们分析自然突变对导致17号染色体相关额颞叶痴呆（FTDP - 17）的tau蛋白的影响。最后，我们考虑tau蛋白的积累或其构象变化是否与tau蛋白诱导的神经退行性变有关，并提出神经退行性变的机制。
