title: A new brain metalloendopeptidase which degrades the Alzheimer beta-amyloid 1-40 peptide producing soluble fragments without neurotoxic effects.
abstract: A new metalloendopeptidase was purified to apparent homogeneity from a homogenate of normal human brain using successive steps of chromatography on DEAE-Trisacryl, hydroxylapatite and Sephacryl S-200. The purified enzyme cleaved the Gly33-Leu34 bond of the 25-35 neurotoxic sequence of the Alzheimer beta-amyloid 1-40 peptide producing soluble fragments without neurotoxic effects. This enzyme activity was only inhibited by divalent cation chelators such as EDTA, EGTA and o-phenanthroline (1 mM) and was insensitive to phosphoramidon and captopril (1 microM concentration), specific inhibitors of neutral endopeptidase (EC 3.4.24.11) and angiotensin-converting enzyme (EC 3.4.15.1), respectively. The high affinity of this human brain endopeptidase for beta-amyloid 1-40 peptide (Km = 5 microM) suggests that it may play a physiological role in the degradation of this substance produced by normal cellular metabolism. It may also be hypothesized that the abnormal accumulation of the amyloid beta-protein in Alzheimer's disease may be initiated by a defect or an inactivation of this enzyme.
authors.affiliation: Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Fortaleza, Brasil.
authors.forename: K M
authors.initials: KM
authors.lastname: Carvalho
authors.forename: M S
authors.initials: MS
authors.lastname: França
authors.forename: G C
authors.initials: GC
authors.lastname: Camarão
authors.forename: A F
authors.initials: AF
authors.lastname: Ruchon
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000201:enzymology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000201:enzymology*; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans
chemical_list: D016229:Amyloid beta-Peptides; D010450:Endopeptidases