MISC

2009年

Destruxin E Decreases Beta-Amyloid Generation by Reducing Colocalization of Beta-Amyloid-Cleaving Enzyme 1 and Beta-Amyloid Protein Precursor

NEURODEGENERATIVE DISEASES
  • Naohiro Itoh
  • ,
  • Masayasu Okochi
  • ,
  • Shinji Tagami
  • ,
  • Kouhei Nishitomi
  • ,
  • Taisuke Nakayama
  • ,
  • Kanta Yanagida
  • ,
  • Akio Fukumori
  • ,
  • Jingwei Jiang
  • ,
  • Kohji Mori
  • ,
  • Motoko Hosono
  • ,
  • Jyunko Kikuchi
  • ,
  • Yuko Nakano
  • ,
  • Yoshihiko Takinami
  • ,
  • Keiji Dohi
  • ,
  • Atsuko Nishigaki
  • ,
  • Hiroshi Takemoto
  • ,
  • Kazuyuki Minagawa
  • ,
  • Takaaki Katoh
  • ,
  • Michael Willem
  • ,
  • Christian Haass
  • ,
  • Takashi Morihara
  • ,
  • Toshihisa Tanaka
  • ,
  • Takashi Kudo
  • ,
  • Hiroshi Hasegawa
  • ,
  • Masaki Nishimura
  • ,
  • Gaku Sakaguchi
  • ,
  • Akira Kato
  • ,
  • Masatoshi Takeda

6
5-6
開始ページ
230
終了ページ
239
記述言語
英語
掲載種別
DOI
10.1159/000236902
出版者・発行元
KARGER

Alzheimer-disease-associated beta-amyloid (A beta) is produced by sequential endoproteolysis of beta-amyloid protein precursor (beta APP): the extracellular portion is shed by cleavage in the juxtamembrane region by beta-amyloid-cleaving enzyme (BACE)/beta-secretase, after which it is cleaved by presenilin (PS)/gamma-secretase near the middle of the transmembrane domain. Thus, inhibition of either of the secretases reduces A beta generation and is a fundamental strategy for the development of drugs to prevent Alzheimer disease. However, it is not clear how small compounds reduce A beta production without inhibition of the secretases. Such compounds are expected to avoid some of the side effects of secretase inhibitors. Here, we report that destruxin E (Dx-E), a natural cyclic hexadepsipeptide, reduces A beta generation without affecting BACE or PS/gamma-secretase activity. In agreement with this, Dx-E did not inhibit Notch signaling. We found that Dx-E decreases colocalization of BACE1 and beta APP, which reduces beta-cleavage of beta APP. Therefore, the data demonstrate that Dx-E represents a novel A beta-reducing process which could have fewer side effects than secretase inhibitors. Copyright (C) 2009 S. Karger AG, Basel

Web of Science ® 被引用回数 : 6

リンク情報
DOI
https://doi.org/10.1159/000236902
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000274466900004&DestApp=WOS_CPL

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