Discovery of Chemical Compounds That Induce Degradation of APP Beta-CTF

Alzheimer’s disease (AD) is a neurodegenerative disorder that affects more than 5 million people in the United States. One of the hallmarks of AD is the accumulation of amyloid plaques in the brain of patients. The amyloid plaque is composed of beta amyloid (Abeta) peptide, which originates from an amyloid precursor protein (APP). Multiple lines of evidence suggest that a defective clearance mechanism is involved in the pathogenesis of Alzheimer’s disease. Our laboratory has discovered a novel molecular pathway regulating protein clearance, which represents an attractive therapeutic target for developing drugs for Alzheimer’s disease.

We seek to build on our screen of a chemical library of small molecules that identified compounds that increase the clearance of the amyloid beta peptide. This project represents a direct effort to search for small molecule compounds that can restore protein clearance.