MISC

2001年5月25日

Metabolic regulation of brain Aβ by neprilysin

Science
  • N. Iwata
  • ,
  • S. Tsubuki
  • ,
  • Y. Takaki
  • ,
  • K. Shirotani
  • ,
  • B. Lu
  • ,
  • N. P. Gerard
  • ,
  • C. Gerard
  • ,
  • E. Hama
  • ,
  • H. J. Lee
  • ,
  • T. C. Saido

292
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.

リンク情報
DOI
https://doi.org/10.1126/science.1059946
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/11375493
ID情報
  • DOI : 10.1126/science.1059946
  • ISSN : 0036-8075
  • PubMed ID : 11375493
  • SCOPUS ID : 0035947207

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