Small Molecule Regulation of a Protein Quality Control E3 to Treat PSP 

Principal Investigator: Kenneth Matthew Scaglione, PhD
Molecular Genetics and Microbiology, Duke University

Durham, NC 

One hallmark of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD)is the accumulation of abnormal deposit of the tau protein in cells in the brain.  This deposition of tau correlates with dysfunction and eventual death of brain cells.  Therefore, one way to treat PSP is to remove the tau protein so that it cannot cause problems in the brain.  One way to accomplish this is to turn on pathways in cells that stimulate the removal of tau.  One protein, C-terminus of Hsc70 Interacting Protein (CHIP) functions to accelerate the removal of tau. The goal of this proposal is to identify compounds that stimulate CHIP function and to determine if these compounds accelerate the removal of tau.  Successful completion of the goals of this grant will result in first-in-class compounds that activate CHIP and promote the clearance of tau. We believe these are important first steps towards developing small molecules that may be beneficial for patients that suffer from PSP and CBD.