LRP Internalizes FXIa Complexed to APP, PN1 :Effect on AB

Project Summary

LDL Receptor Related Protein (LRP) is a receptor on the cell surface that takes in the amyloid precursor protein (APP) so it can be broken down. Determining the role of LRP in this process is key to understanding how amyloid beta deposits are formed. Dr. Knauer has proposed that the metabolic process causing protein deposits to form occurs inside of cells, but is triggered by molecules outside of the cell called proteases. These proteases modify the amyloid protein that causes AD and also cause it to rapidly enter cells where it can set off a process that results in damaging deposits accumulating outside of cells. To test this hypothesis, Dr. Knauer is working to identify an inhibitor of these proteases that her laboratory recently discovered and determine to what extent it can contribute to, or reduce, the formation of deposits or "senile plaques." She will test the effectiveness of protease inhibitors on limiting the metabolic pathway that gives rise to deposits in order to search for the exact point of entry in this pathway. If this process can be elucidated, drugs may be developed to block the entry of amyloid protein into cells and inhibit the metabolic process that causes deposits to form.