title: Biochemical identification of the neutral endopeptidase family member responsible for the catabolism of amyloid beta peptide in the brain.
abstract: Amyloid beta peptide (Abeta) is a physiological peptide that is constantly catabolized in the brain. We previously demonstrated that an endopeptidase sensitive to phosphoramidon and thiorphan conducts the initial rate-limiting proteolysis of Abeta in vivo, but the exact molecular identity of the peptidase(s) has remained unknown because of the molecular redundancy of such activity. We analyzed the brain-derived enzyme by means of immuno-depletion and gene disruption, and demonstrate here that neprilysin accounts for the majority of the Abeta-degrading activity. Furthermore, kinetic analysis, giving a K(m) value of 2.8 +/- 0.76 microM, indicated that Abeta(1-42) is a relevant substrate for neprilysin.
authors.affiliation: Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan. ytaka@brain.riken.go.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Takaki
authors.forename: N
authors.initials: N
authors.lastname: Iwata
authors.forename: S
authors.initials: S
authors.lastname: Tsubuki
authors.forename: S
authors.initials: S
authors.lastname: Taniguchi
authors.forename: S
authors.initials: S
authors.lastname: Toyoshima
authors.forename: B
authors.initials: B
authors.lastname: Lu
authors.forename: N P
authors.initials: NP
authors.lastname: Gerard
authors.forename: C
authors.initials: C
authors.lastname: Gerard
authors.forename: H J
authors.initials: HJ
authors.lastname: Lee
authors.forename: K
authors.initials: K
authors.lastname: Shirotani
authors.forename: T C
authors.initials: TC
authors.lastname: Saido
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D002852:Chromatography, Ion Exchange; D006868:Hydrolysis; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D015260:Neprilysin / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D015260:Neprilysin