Mar
Gamma secretase modulators have shown promise in Alzheimer’s disease animal model efficacy studies, according to research conducted by TorreyPines Therapeutics, Inc..
Presented by Steven Wagner, Ph.D., the company’s Chief Scientific Officer, at the recent Keystone Symposium>Alzheimer’s disease make a greater proportion of the longer Ab peptides, especially Ab42, relative to unaffected individuals. All of these Ab peptides, including the pathogenic Ab42 peptide, are derived via proteolysis from a much larger precursor molecule known as the amyloid b precursor protein (APP).
During normal catabolism, two crucial enzymes, or proteases, are responsible for generating these Ab peptides from APP. The first enzyme, beta secretase (b-secretase), cuts the APP molecule into two major pieces comprised of a soluble extracellular fragment and a membrane-associated fragment. The second enzyme, gamma secretase (g-secretase), then cleaves the membrane- associated fragment into one of several different Ab peptides that vary in length from 34 to 42 amino acids.