title: Gamma-secretase--intramembrane protease with a complex.
abstract: Gamma-secretase catalyzes intramembrane proteolysis of the amyloid beta protein precursor, a process closely linked to the development of Alzheimer's disease. This protease also cleaves the transmembrane domain of the Notch receptor as part of a signaling pathway that is essential for proper embryonic development. Recent findings suggest that gamma-secretase is a complex of at least four integral membrane proteins: presenilin, nicastrin, Aph-1, and Pen-2. Assembly of these four components apparently leads to autocleavage of presenilin into two subunits that together compose the intramembranous active site of gamma-secretase. Understanding the mechanism of this unusual enzyme is important, as it is both a key therapeutic target and a founding member of a newly discovered class of intramembrane-cleaving proteases.
authors.affiliation: Center for Neurologic Diseases at Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. mwolfe@rics.bwh.harvard.edu.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Wolfe
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology; D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D010450:Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000201:enzymology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism; D053764:Presenilin-1; D053766:Presenilin-2; D051880:Receptors, Notch
chemical_list: D016564:Amyloid beta-Protein Precursor; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009097:Multienzyme Complexes; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D051880:Receptors, Notch; C413604:nicastrin protein; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human