2001年5月25日
Metabolic regulation of brain Aβ by neprilysin
Science
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- 巻
- 292
- 号
- 5521
- 開始ページ
- 1550
- 終了ページ
- 1552
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1126/science.1059946
Amyloid β peptide (Aβ), the pathogenic agent of Alzheimer's disease (AD), is a physiological metabolite in the brain. We examined the role of neprilysin, a candidate Aβ-degrading peptidase, in the metabolism using neprilysin genedisrupted mice. Neprilysin deficiency resulted in defects both in the degradation of exogenously adrninistered Aβ and in the metabolic suppression of the endogenous Aβ levels in a gene dose-dependent manner. The regional levels of Aβ in the neprilysin-deficient mouse brain were in the distinct order of hippocampus, cortex, thalamus/striatum, and cerebellum, where hippocampus has the highest level and cerebellum the lowest, correlating with the vulnerability to Aβ deposition in brains of humans with AD. Our observations suggest that even partial down-regulation of neprilysin activity, which could be caused by aging, can contribute to AD development by promoting Aβ accumulation.
- ID情報
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- DOI : 10.1126/science.1059946
- ISSN : 0036-8075
- PubMed ID : 11375493
- SCOPUS ID : 0035947207