Tau, tau kinases, and tauopathies: An updated overview

Tau is a macrotubule-associated protein primarily involved in the stabilization of the cytoskeleton. Under normal conditions, phosphorylation reduces the affinity of tau for tubulin, allowing the protein to detach from microtubules and ensuring the system dynamics in neuronal cells. However, hyperphosphorylated tau aggregates into paired helical filaments, the main constituents of neurofibrillary tangles found in the brains of patients with Alzheimer's disease and other tauopathies. In this review, we provide an overview of the structure of tau and the pathophysiological roles of tau phosphorylation. We also evaluate the major protein kinases involved and discuss the progress made in the development of drug therapies aimed at inhibiting tau kinases.

Automated summary

Tau is a macrotubule-associated protein that plays a crucial role in stabilizing the cytoskeleton. While phosphorylation normally decreases tau's affinity for microtubules, hyperphosphorylated tau forms aggregates that contribute to the development of neurofibrillary tangles in Alzheimer's disease and other tauopathies. This review provides an overview of tau's structure and the pathophysiological effects of tau phosphorylation, as well as the progress in developing drug therapies targeting tau kinases.