PROTAC is discovered that by utilizing the body's natural protein cleaning system, it is possible to reduce protein levels rather than inhibit protein functions. As opposed to traditional small molecule inhibitors and antagonists, which inhibit protein function via the occupation drive mode of action, PROTAC plays a therapeutic role by inducing the degradation of pathogenic target proteins.
There are some examples of PROTACs in neurological disease treatment have been reported. For example, PROTACs with the E3 ubiquitin ligase-binding ligand (such as lenalidomide or thalidomide) can be combined with the Tau protein and subsequently induce tau ubiquitination and facilitate its degradation in cells. As tau aggregation, especially hyperphosphorylated tau, leads to tauopathies in AD, tau or any form of post-translational modification is targeted and E3 ubiquitin ligases such as Cereblon are recruited to ubiquitinate tau to mark it for degradation. Thus, PROTACs have promise for the treatment of neurodegenerative diseases, acting by targeting and promoting the degradation of disease-associated proteins.
