Biochemical identification of the neutral endopeptidase family member responsible for the catabolism of amyloid beta peptide in the brain.

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.

journal_name

J Biochem

journal_title

Journal of biochemistry

authors

Takaki Y,Iwata N,Tsubuki S,Taniguchi S,Toyoshima S,Lu B,Gerard NP,Gerard C,Lee HJ,Shirotani K,Saido TC

doi

10.1093/oxfordjournals.jbchem.a022839

keywords:

subject

Has Abstract

pub_date

2000-12-01 00:00:00

pages

897-902

issue

6

eissn

0021-924X

issn

1756-2651

journal_volume

128

pub_type

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