title: Blocking the cleavage at midportion between gamma- and epsilon-sites remarkably suppresses the generation of amyloid beta-protein.
abstract: To examine how gamma- and epsilon-cleavages of beta-amyloid precursor protein (APP) are related, each cleavage site was replaced with a stretch of Trp that cannot be cleaved by gamma-secretase. Replacement of the gamma- or epsilon-site significantly suppressed secretion of amyloid beta-protein (Abeta), and produced longer Abeta or longer APP intracellular domain, respectively. This cleavage at the midportion between gamma- and epsilon-sites was also gamma-secretase-dependent. Blocking this cleavage with a Trp stretch remarkably suppressed Abeta generation, indicating that the midportion cleavage is required for the generation of Abeta.
authors.affiliation: Department of Neuropathology, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Sato
authors.forename: Yu
authors.initials: Y
authors.lastname: Tanimura
authors.forename: Naoko
authors.initials: N
authors.lastname: Hirotani
authors.forename: Takaomi C
authors.initials: TC
authors.lastname: Saido
authors.forename: Maho
authors.initials: M
authors.lastname: Morishima-Kawashima
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ihara
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D017077:Culture Media, Conditioned; D006868:Hydrolysis; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
chemical_list: D016229:Amyloid beta-Peptides; D017077:Culture Media, Conditioned