Post-Translational Modifications in Tau and Their Roles in Alzheimer's Pathology


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Abstract

: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.

About the authors

Subha Kalyaanamoorthy

Department of Chemistry, University of Waterloo

Author for correspondence.
Email: info@benthamscience.net

Stanley Kojo Opare

Department of Chemistry, University of Waterloo

Email: info@benthamscience.net

Xiaoxiao Xu

Chemistry, University of Waterloo

Email: info@benthamscience.net

Aravindhan Ganesan

Department of Chemistry, University of Waterloo

Email: info@benthamscience.net

Praveen Rao

Department of Chemistry, University of Waterloo

Email: info@benthamscience.net

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