for the design of tau binders that can be used as part of the PROteolysis TArgeting Chimeras (PROTACs) approach. PROTACs is a strategy to degrade proteins by hijacking the ubiquitin-proteasome system (UPS). PROTAC is a bifunctional-hybrid molecule that on one side binds to E3 ubiquitin ligase and on the other side to a target protein. This bifunctional binder allows exposed lysine on the target protein to be ubiquitinated by the E3 ubiquitin ligase complex, followed by UPS-mediated protein degradation of aberrant tau in frontotemporal dementia patient-derived neuronal cell models [124,125].
