Targeting Tau Protein with Proximity Inducing Modulators: A New Frontier to Combat Tauopathies

Dysregulation of correct protein tau homeostasis represents the seed for the development of several devastating central nervous system disorders, known as tauopathies, that affect millions of people worldwide. Despite massive public and private support to research funding, these diseases still represent unmet medical needs. In fact, the tau-targeting tools developed to date have failed to translate into the clinic. Recently, taking advantage of the modes that nature uses to mediate the flow of information in cells, researchers have developed a new class of molecules, called proximity-inducing modulators, which exploit spatial proximity to modulate protein function(s) and redirect cellular processes. In this perspective, after a brief discussion about tau protein and the classic tau-targeting approaches, we will discuss the different classes of proximity-inducing modulators developed so far and highlight the applications to modulate tau protein's function and tau-induced toxicity.