Title:Post-Translational Modifications in Tau and Their Roles in Alzheimer's
Pathology
Volume: 21
Issue: 1
关键词:
阿尔茨海默病，tau蛋白，翻译后修饰，磷酸化，乙酰化，甲基化，硝化，糖基化，糖基化，截断，脱酰胺，泛素化，聚合化，计算建模，治疗方法。
摘要: Microtubule-Associated Protein Tau (also known as tau) has been shown to accumulate
into paired helical filaments and neurofibrillary tangles, which are known hallmarks of
Alzheimer’s disease (AD) pathology. Decades of research have shown that tau protein undergoes
extensive post-translational modifications (PTMs), which can alter the protein's structure, function,
and dynamics and impact the various properties such as solubility, aggregation, localization,
and homeostasis. There is a vast amount of information describing the impact and role of different
PTMs in AD pathology and neuroprotection. However, the complex interplay between these
PTMs remains elusive. Therefore, in this review, we aim to comprehend the key post-translational
modifications occurring in tau and summarize potential connections to clarify their impact on the
physiology and pathophysiology of tau. Further, we describe how different computational modeling
methods have helped in understanding the impact of PTMs on the structure and functions of
the tau protein. Finally, we highlight the tau PTM-related therapeutics strategies that are explored
for the development of AD therapy.
