Beharry Cindy, Cohen Leah S, Di Jing, Ibrahim Kawsar, Briffa-Mirabella Susan, Alonso Alejandra del C
Department of Biology and Center for Developmental Neuroscience, College of Staten Island, Graduate Center, The City University of New York, Staten Island, NY, 10314, USA.
Neurosci Bull. 2014 Apr;30(2):346-58. doi: 10.1007/s12264-013-1414-z. Epub 2014 Apr 15.
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 functions in microtubule assembly and stabilization and with regard to its interactions with other proteins. We describe and analyze important post-translational modifications: hyperphosphorylation, ubiquitination, glycation, glycosylation, nitration, polyamination, proteolysis, acetylation, and methylation. We discuss how these post-translational modifications can alter tau's biological function. We analyze the role of mitochondrial health in neurodegeneration. We propose that microtubules could be a therapeutic target and review different approaches. Finally, we consider whether tau accumulation or its conformational change is related to tau-induced neurodegeneration, and 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是一种脑微管相关蛋白。在此，我们讨论tau在微管组装和稳定中的功能，以及它与其他蛋白质的相互作用。我们描述并分析重要的翻译后修饰：高度磷酸化、泛素化、糖基化终产物形成、糖基化、硝化、多胺化、蛋白水解、乙酰化和甲基化。我们讨论这些翻译后修饰如何改变tau的生物学功能。我们分析线粒体健康在神经退行性变中的作用。我们提出微管可能是一个治疗靶点，并综述不同的方法。最后，我们考虑tau积累或其构象变化是否与tau诱导的神经退行性变有关，并提出一种神经退行性变的机制。
