Tau protein structure and dynamics.

Abstract

Alzheimer's disease (AD) is the most common type of dementia. It is characterized by chronic memory defects, alterations in behavior, and cognitive decline. AD is histopathologically characterized by two hallmarks: intracellular accumulation of Tau protein as neurofibrillary tangles (NFTs) and extracellular deposition of amyloid beta. In this book chapter, we highlighted the microtubule-associated protein Tau, exploring its structural diversity and its distinct isoforms. It is an intrinsically disordered protein which lacks three-dimensional structure that are defined by their vast structural segments that undergo rapid and prolonged conformational alterations. It has not been possible to analyze the structure of disordered proteins since they often have different conformations and are very flexible. Tau proteins comprise various domains that significantly participate in physiology in neurons, including stabilizing microtubule structure and dynamics and axonal cargo transport. In its physiological state, Tau interacts with various molecules and proteins. By various post-translational modifications at specific sites in Tau protein, including phosphorylation, acetylation, and methylation. Tau protein undergo pathological structural confirmation by hyperphosphorylation, forming insoluble oligomers, and developing as paired helical filaments. Finally, as the disease progressed, it accumulated inside the neurons as NFTs.