title: gamma-Secretase can cleave amyloid precursor protein fragments independent of alpha- and beta-secretase pre-cutting.
abstract: Abeta is the major component of amyloid in the brain in Alzheimer's disease and is derived from an amyloid precursor protein (APP) by the sequential proteolytic processing of two putative proteases, called beta- and gamma-secretase. To clarify the mechanism of gamma-secretase processing, we created constructs contained the C-terminal domain of APP and analyzed the processing in COS-1 cells. We found that C-terminal fragments (CTFs) containing a short extra N-terminal region before the beta-secretase cleavage site were directly processed at gamma-secretase cleavage site. This suggests that gamma-secretase cleavage occurs independently and is not dependent on alpha- and beta-secretase cleavage.
authors.affiliation: Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo 156-8585, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kume
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sekijima
authors.forename: Kei
authors.initials: K
authors.lastname: Maruyama
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Kametani
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D010450:Endopeptidases / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics; D010455:Peptides / Q000378:metabolism*; D053764:Presenilin-1
chemical_list: D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; D010455:Peptides; D053764:Presenilin-1; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases