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A new brain metalloendopeptidase which degrades the Alzheimer ?-amyloid 1-40 peptide producing soluble fragments without neurotoxic effects

DOI: 10.1590/S0100-879X1997001000002

Keywords: brain metalloendopeptidase, alzheimer ?-amyloid 1-40 peptide, alzheimer's disease.

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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 μm concentration), specific inhibitors of neutral endopeptidase (ec and angiotensin-converting enzyme (ec, respectively. the high affinity of this human brain endopeptidase for ?-amyloid 1-40 peptide (km = 5 μm) 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.


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