Identification of the major A beta(1-42)-degrading catabolic pathway in brain parenchyma: Suppression leads to biochemical and pathological deposition

Authors
Iwata, N Tsubuki, S Takaki, Y Watanabe, K Sekiguchi, M Hosoki, E Kawashima-Morishima, M Lee, HJ Hama, E Sekine-Aizawa, Y Saido, TC
Citation
N. Iwata et al., Identification of the major A beta(1-42)-degrading catabolic pathway in brain parenchyma: Suppression leads to biochemical and pathological deposition, NAT MED, 6(2), 2000, pp. 143-150
Citations number
34
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Journal title
NATURE MEDICINE
ISSN journal
10788956 → ACNP
Volume
6
Issue
2
Year of publication
2000
Pages
143 - 150
Database
ISI
SICI code
1078-8956(200002)6:2<143:IOTMAB>2.0.ZU;2-D
Abstract
Alzheimer amyloid beta-peptide (A beta) is a physiological peptide constant ly anabolized and catabolized under normal conditions. We investigated the mechanism of catabolism by tracing multiple-radiolabeled synthetic peptide injected into rat hippocampus. The A beta(1-42) peptide underwent full degr adation through limited proteolysis conducted by neutral endopeptidase (NEP ) similar or identical to neprilysin as biochemically analyzed. Consistentl y, NEP inhibitor infusion resulted in both biochemical and pathological dep osition of endogenous A beta(42) in brain. This NEP-catalyzed proteolysis t herefore limits the rate of A beta(42) catabolism, up-regulation of which c ould reduce the risk of developing Alzheimer's disease by preventing A beta accumulation.