Title: β-Secretase as a Therapeutic Target for Inhibitor Drugs
Volume: 9
Issue: 11
Author(s): Arun K. Ghosh, Lin Hong and Jordan Tang
Affiliation:
Keywords:
beta secretase, beta secretase and inhibitor, memapsin 2, asp-2
Abstract: Recent identification of β-scretasse being a membrane-associated aspartic protease has stimulated strong interest on this enzyme as a therapeutic target for Alzheimers disease. Here we review the current understanding in the structure-function relationship as well as the status in the design of its inhibitors of this protease, memapsin 2 (BACE, ASP-2). The development in the basic tools, such as the preparation of recombinant memapsin 2, the assay method for kinetic measurements of inhibition, the determination of the subsite specificity and the crystal structure of memapsin 2 complexed to a tight-binding inhibitor, has made the structural based inhibitor design possible. More recent inhibitors, having Ki values in the nanomolar range and molecular size in low 700 Da, show some promise that clinically useful inhibitors of β-scretasse may be attainable.
