Angiotensin-converting Enzyme Converts Amyloid Beta-protein 1-42 (Abeta(1-42)) to Abeta(1-40), and Its Inhibition Enhances Brain Abeta Deposition

Overview

Journal J Neurosci

Specialty Neurology

Date 2007 Aug 10

PMID 17687040

Citations 79

Authors

Kun Zou

Haruyasu Yamaguchi

Hiroyasu Akatsu

Takaaki Sakamoto

Mihee Ko

Kazushige Mizoguchi

Jian-Sheng Gong

Wenxin Yu

Takayuki Yamamoto

Kenji Kosaka

Katsuhiko Yanagisawa

Makoto Michikawa

Affiliations

Soon will be listed here.

Abstract

The abnormal deposition of the amyloid beta-protein (Abeta) in the brain appears crucial to the pathogenesis of Alzheimer's disease (AD). Recent studies have suggested that highly amyloidogenic Abeta(1-42) is a cause of neuronal damage leading to AD pathogenesis and that monomeric Abeta(1-40) has less neurotoxicity than Abeta(1-42). We found that mouse and human brain homogenates exhibit an enzyme activity converting Abeta(1-42) to Abeta(1-40) and that the major part of this converting activity is mediated by the angiotensin-converting enzyme (ACE). Purified human ACE converts Abeta(1-42) to Abeta(1-40) as well as decreases Abeta(1-42)/Abeta(1-40) ratio and degrades Abeta(1-42) and Abeta(1-40). Importantly, the treatment of Tg2576 mice with an ACE inhibitor, captopril, promotes predominant Abeta(1-42) deposition in the brain, suggesting that ACE regulates Abeta(1-42)/Abeta(1-40) ratio in vivo by converting secreted Abeta(1-42) to Abeta(1-40) and degrading Abetas. The upregulation of ACE activity can be a novel therapeutic strategy for AD.

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