論文

査読有り
2015年2月

Midazolam inhibits the formation of amyloid fibrils and GM1 ganglioside-rich microdomains in presynaptic membranes through the gamma-aminobutyric acid A receptor

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
  • Naoki Yamamoto
  • ,
  • Hajime Arima
  • ,
  • Takeshi Sugiura
  • ,
  • Hiroyuki Hirate
  • ,
  • Nobuyoshi Kusama
  • ,
  • Kenji Suzuki
  • ,
  • Kazuya Sobue

457
4
開始ページ
547
終了ページ
553
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.bbrc.2015.01.022
出版者・発行元
ACADEMIC PRESS INC ELSEVIER SCIENCE

Recent studies have suggested that a positive correlation exists between surgical interventions performed under general anesthesia and the risk of developing Alzheimer's disease (AD) in the late postoperative period. It has been reported that amyloid beta-protein (A beta) fibrillogenesis, which is closely related to AD, is accelerated by exposure to anesthetics. However, the mechanisms underlying these effects remain uncertain. This study was designed to investigate whether the anesthetic midazolam affects A beta fibrillogenesis, and if so, whether it acts through GM! ganglioside (GM1) on the neuronal surface. Midazolam treatment decreased GM1 expression in the detergent-resistant membrane microdomains of neurons, and these effects were regulated by the gamma-aminobutyric acid-A receptor. Midazolam inhibited A beta fibril formation from soluble A beta on the neuronal surface. In addition, midazolam suppressed GM1-induced fibril formation in a cell-free system. Moreover, midazolam inhibited the formation of All assemblies in synaptosomes isolated from aged mouse brains. These finding suggested that midazolam has direct and indirect inhibitory effects on A beta fibrillogenesis. (C) 2015 Elsevier Inc. All rights reserved.

Web of Science ® 被引用回数 : 9

リンク情報
DOI
https://doi.org/10.1016/j.bbrc.2015.01.022
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25600806
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000350838800010&DestApp=WOS_CPL

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