Tau; One Protein, So Many Diseases

Simple Summary Tau is an important protein for maintaining the shape and normal function of nerve cells. There are many diseases that are identified by changes in this protein, yet examination of tau in these diseases shows robust differences in tau modifications. A question arises from these observations on whether tau can be used as a therapeutic target. In this review, we aimed to provide a general overview of tau-physiology and pathophysiology in neurodegenerative diseases and describe the current approaches for diagnosis and experimental/clinical trials. This review is intended to enhance the understanding of graduate students specializing in neurobiology. Tau, a member of the microtubule-associated proteins, is a known component of the neuronal cytoskeleton; however, in the brain tissue, it is involved in other vital functions beyond maintaining the cellular architecture. The pathologic tau forms aggregates inside the neurons and ultimately forms the neurofibrillary tangles. Intracellular and extracellular accumulation of different tau isoforms, including dimers, oligomers, paired helical filaments and tangles, lead to a highly heterogenous group of diseases named "Tauopathies". About twenty-six different types of tauopathy diseases have been identified that have different clinical phenotypes or pathophysiological characteristics. Although all these diseases are identified by tau aggregation, they are distinguishable based on the specific tau isoforms, the affected cell types and the brain regions. The neuropathological and phenotypical heterogeneity of these diseases impose significant challenges for discovering new diagnostic and therapeutic strategies. Here, we review the recent literature on tau protein and the pathophysiological mechanisms of tauopathies. This article mainly focuses on physiologic and pathologic tau and aims to summarize the upstream and downstream events and discuss the current diagnostic approaches and therapeutic strategies.