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

被引：85

作者：

Takaki, Y

Iwata, N

Tsubuki, S

Taniguchi, S

Toyoshima, S

Lu, B

Gerard, NP

Gerard, C

Lee, HJ

Shirotani, K

Saido, TC ^{[1
]}

机构：

[1] RIKEN, Brain Sci Inst, Lab Proteolyt Neurosci, Wako, Saitama 3510198, Japan

[2] Hoshi Univ, Fac Pharmaceut Sci, Dept Biochem, Tokyo 1428501, Japan

[3] Harvard Univ, Sch Med, Dept Pediat & Med, Boston, MA 02115 USA

来源：

JOURNAL OF BIOCHEMISTRY | 2000年 / 128卷 / 06期

关键词：

Alzheimer's disease; amyloid beta peptide; catabolism; neprilysin; neutral endopeptidase;

D O I：

10.1093/oxfordjournals.jbchem.a022839

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Amyloid beta peptide (A beta) 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 A beta 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 immune-depletion and gene disruption, and demonstrate here that neprilysin accounts for the majority of the A beta -degrading activity. Furthermore, kinetic analysis, giving a K-m value of 2.8 +/- 0.76 muM, indicated that A beta (1-42) is a relevant substrate for neprilysin.

引用

页码：897 / 902

页数：6

共 32 条

[1] Association of CD10 neutral endopeptidase 24.11 with membrane microdomains rich in glycosylphosphatidylinositol-anchored proteins and Lyn kinase [J].