title: Proteolytic processing of presenilin-1 (PS-1) is not associated with Alzheimer's disease with or without PS-1 mutations.
abstract: Cerebral presenilin-1 protein (PS-1) is normally composed of the amino-terminal fragment (NTF) with Mr 28 kDa and the carboxy-terminal fragment (CTF) with 18 kDa. We analyzed human PS-1 in brains with early-onset familial Alzheimer's disease (FAD) with and without PS-1 mutations to study whether mutated PS-1 was abnormally metabolized. Cerebral PS-1 were found to be cleaved into two fragments of NTF and CTF independently of the occurrence of PS-1 mutation in human brains. A small portion of PS-1 was recently found to suffer another processing by caspase-3, an apoptosis-related cysteine protease. In contrast to the recent finding that the Volga-German mutation on presenilin-2 (PS-2) affects the increasing caspase-3 PS-2 fragment, the PS-1 mutation did not cause a significant change in PS-1 fragmentation. We conclude that PS-1 fragmentation and other (probably caspase-3-mediated) digestion following apoptosis occur independently of PS-1 mutations.
authors.affiliation: Department of Molecular Biology, Tokyo Institute of Psychiatry, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Okochi
authors.forename: K
authors.initials: K
authors.lastname: Ishii
authors.forename: M
authors.initials: M
authors.lastname: Usami
authors.forename: N
authors.initials: N
authors.lastname: Sahara
authors.forename: F
authors.initials: F
authors.lastname: Kametani
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: P E
authors.initials: PE
authors.lastname: Fraser
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: A M
authors.initials: AM
authors.lastname: Saunders
authors.forename: L
authors.initials: L
authors.lastname: Hendriks
authors.forename: S I
authors.initials: SI
authors.lastname: Shoji
authors.forename: L E
authors.initials: LE
authors.lastname: Nee
authors.forename: J J
authors.initials: JJ
authors.lastname: Martin
authors.forename: C
authors.initials: C
authors.lastname: Van Broeckhoven
authors.forename: P H
authors.initials: PH
authors.lastname: St George-Hyslop
authors.forename: A D
authors.initials: AD
authors.lastname: Roses
authors.forename: H
authors.initials: H
authors.lastname: Mori
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D017354:Point Mutation; D053764:Presenilin-1; D011499:Protein Processing, Post-Translational; D011817:Rabbits
chemical_list: D008565:Membrane Proteins; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1