title: gamma-Secretase in biology and medicine.
abstract: gamma-Secretase is a membrane-embedded proteolytic complex composed of presenilin and three other subunits. The gamma-secretase complex generates the amyloid beta-peptide of Alzheimer's disease but also plays important roles in normal physiology, especially in signaling from the Notch receptor. How this hydrolytic enzyme works in a hydrophobic environment is largely unanswered, but mutagenesis and chemical probes have offered insight. gamma-Secretase is an important therapeutic target, although mechanism-based toxicity presents a serious obstacle. Agents that lower amyloid beta-peptide production while leaving important normal functions of gamma-secretase intact are promising therapeutic leads. Inhibition of Notch signaling by gamma-secretase inhibitors, which is undesirable for the prevention or treatment of Alzheimer's disease, may be beneficial for the treatment of a variety of cancers.
authors.affiliation: Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Boston, MA 02115 USA. mwolfe@rics.bwh.harvard.edu
authors.forename: Michael S
authors.initials: MS
authors.lastname: Wolfe
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology*; D053829:Amyloid Precursor Protein Secretases / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D004364:Pharmaceutical Preparations
chemical_list: D004364:Pharmaceutical Preparations; D053829:Amyloid Precursor Protein Secretases