%0 Journal Article
%T A new brain metalloendopeptidase which degrades the Alzheimer £¿-amyloid 1-40 peptide producing soluble fragments without neurotoxic effects
%A Carvalho
%A K.M.
%A Fran£¿a
%A M.S.F.
%A Camar£¿o
%A G.C.
%A Ruchon
%A A.F.
%J Brazilian Journal of Medical and Biological Research
%D 1997
%I Associa??o Brasileira de Divulga??o Cient¨ªfica
%R 10.1590/S0100-879X1997001000002
%X 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 £¿-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 ¦Ìm 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 £¿-amyloid 1-40 peptide (km = 5 ¦Ìm) 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 £¿-protein in alzheimer's disease may be initiated by a defect or an inactivation of this enzyme.
%K brain metalloendopeptidase
%K alzheimer £¿-amyloid 1-40 peptide
%K alzheimer's disease.
%U http://www.scielo.br/scielo.php?script=sci_abstract&pid=S0100-879X1997001000002&lng=en&nrm=iso&tlng=en