Inhibition of Tau Protein Phosphorylation and Aggregation

Abstract

Tau protein stabilizes microtubules in neuronal cells and maintains cell structure and function [1]. Post-translational modifications of tau, such as phosphorylations, lead to tau detachment from microtubules and subsequent cell death. Modified tau aggregates into cytotoxic structures, leading to neurodegeneration. Currently, neurodegeneration remains without a cure, but several molecular strategies have been employed towards targeting phosphorylation and aggregation of tau protein. Small molecules have been tested as potential aggregation inhibitors. For example, dopamine receptor agonist compounds were effective inhibitors of tau aggregation in vitro [2]. The large molecules, such as antitau antibodies, were also explored for their ability to inhibit phosphorylation of tau or its aggregation. The antitau antibodies, targeting R-repeat epitopes, effectively reduced tau aggregation in vitro [3], and modulated tau phosphorylation by GSK-3β protein kinase [4]. The details regarding the inhibition with various small and large molecules will be described, and new therapeutic strategies discussed.