Fighting Alzheimer's by Cutting Off Amyloid at Its Source

A study in Chemical Communications describes a compound engineered to block the enzyme gamma secretase's production of a precursor protein of amyloid beta, and perhaps prevent the formation of brain plaques that are a hallmark of Alzheimer's disease, reports FierceBiotech . "Historically, drug trials for gamma secretase inhibitors failed because traditional enzyme inhibitors have severe side effects," said Rensselaer Polytechnic Institute Professor Chunyu Wang. "They stopped all of the normal functions of gamma secretase. Our compound binds to the cleavage site of the precursor protein instead of the enzyme itself, which may avoid many problems associated with traditional enzyme inhibitors." Wang sifted through tens of millions of compounds using computer modeling, and eventually pinpointed a "covalent inhibitor" that forms a permanent chemical bond with its target. The so-called C1 inhibitor impedes amyloid production in test tubes and cell culture.