Targeting Protein Aggregates for Autophagosomal Degradation

National Institute Of Neurological Disorders And Stroke

Investigators

Linked publications, trials & patents

Abstract

We have discovered that targeting the upstream autophagy protein FIP200 to different organelles and to protein aggregates can trigger their elimination by autophagy. We aim to engineer small molecules that can bridge FIP200 and Tau aggregates and induce Tau aggregates elimination therapeutically. Our initial drug target is the FIP200 protein, which we have used for drug screening. In collaboration with NCATS at NIH we have identified a series of tool compounds that bind FIP200 and in collaboration with NHLBI we have identified their binding site on FIP200. Further work is ongoing to increase their affinity for FIP200 and initiate proof of concept compounds that can pharmacologically induce selective autophagy.