Drug Discovery

Cognitive Enhancement

Screening for PAI-1 inhibitors to increase plasmin AlphaBeta- degrading activity

Investigator(s): Sidney Strickland, Ph.D.

Institution(s): The Rockefeller University

Duration:

Summary:

A major pathology associated with AD is the deposition of the amyloid-b (Ab) peptide as plaques, within the brain and blood vessels, leading to inflammation and neuronal damage. The deposition of Ab can be traced to overproduction and diminished clearance of this peptide from the brain. One enzyme that has been shown to contribute to clearance of Ab from the brain is plasmin, which is part of the tissue plasminogen activator (tPA) system. This system is compromised in AD due to the elevation of a protein (PAI-1), induced during inflammation. This proposal aims to identify inhibitors of PAI-1 by using a high throughput screening assay. This novel approach may help to increase the efficiency of Ab clearance from the brain. ISOA previously funded work on this project. Good progress was made, initiating the development of a new class of therapies for AD, and justifying follow-on funding.