A new brain metalloendopeptidase which degrades the Alzheimer ß-amyloid 1-40 peptide producing soluble fragments without neurotoxic effects
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 ß-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 3.4.24.11) and angiotensin-converting enzyme (EC 3.4.15.1), respectively. The high affinity of this human brain endopeptidase for ß-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 ß-protein in Alzheimer's disease may be initiated by a defect or an inactivation of this enzyme.
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Associação Brasileira de Divulgação Científica
1997
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oai:scielo:S0100-879X19970010000021998-10-07A new brain metalloendopeptidase which degrades the Alzheimer ß-amyloid 1-40 peptide producing soluble fragments without neurotoxic effectsCarvalho,K.M.França,M.S.F.Camarão,G.C.Ruchon,A.F. brain metalloendopeptidase Alzheimer ß-amyloid 1-40 peptide Alzheimer's disease 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 ß-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 3.4.24.11) and angiotensin-converting enzyme (EC 3.4.15.1), respectively. The high affinity of this human brain endopeptidase for ß-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 ß-protein in Alzheimer's disease may be initiated by a defect or an inactivation of this enzyme.info:eu-repo/semantics/openAccessAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research v.30 n.10 19971997-10-01info:eu-repo/semantics/articletext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X1997001000002en10.1590/S0100-879X1997001000002 |
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Carvalho,K.M. França,M.S.F. Camarão,G.C. Ruchon,A.F. |
| spellingShingle |
Carvalho,K.M. França,M.S.F. Camarão,G.C. Ruchon,A.F. A new brain metalloendopeptidase which degrades the Alzheimer ß-amyloid 1-40 peptide producing soluble fragments without neurotoxic effects |
| author_facet |
Carvalho,K.M. França,M.S.F. Camarão,G.C. Ruchon,A.F. |
| author_sort |
Carvalho,K.M. |
| title |
A new brain metalloendopeptidase which degrades the Alzheimer ß-amyloid 1-40 peptide producing soluble fragments without neurotoxic effects |
| title_short |
A new brain metalloendopeptidase which degrades the Alzheimer ß-amyloid 1-40 peptide producing soluble fragments without neurotoxic effects |
| title_full |
A new brain metalloendopeptidase which degrades the Alzheimer ß-amyloid 1-40 peptide producing soluble fragments without neurotoxic effects |
| title_fullStr |
A new brain metalloendopeptidase which degrades the Alzheimer ß-amyloid 1-40 peptide producing soluble fragments without neurotoxic effects |
| title_full_unstemmed |
A new brain metalloendopeptidase which degrades the Alzheimer ß-amyloid 1-40 peptide producing soluble fragments without neurotoxic effects |
| title_sort |
new brain metalloendopeptidase which degrades the alzheimer ß-amyloid 1-40 peptide producing soluble fragments without neurotoxic effects |
| description |
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 ß-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 3.4.24.11) and angiotensin-converting enzyme (EC 3.4.15.1), respectively. The high affinity of this human brain endopeptidase for ß-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 ß-protein in Alzheimer's disease may be initiated by a defect or an inactivation of this enzyme. |
| publisher |
Associação Brasileira de Divulgação Científica |
| publishDate |
1997 |
| url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X1997001000002 |
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