Biochemical identification of the neutral endopeptidase family member responsible for the catabolism of amyloid beta peptide in the brain |
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Authors: | Takaki Y Iwata N Tsubuki S Taniguchi S Toyoshima S Lu B Gerard N P Gerard C Lee H J Shirotani K Saido T C |
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Institution: | Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan. ytaka@brain.riken.go.jp |
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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. |
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