アルツハイマー病治療に用いられるアセチルコリンエステラーゼ阻害薬の神経保護作用機序に関する研究

DOI DOI Web Site Web Site PubMed 被引用文献6件 参考文献41件 オープンアクセス
  • 高鳥 悠記
    京都大学大学院薬学研究科薬品作用解析学分野

書誌事項

タイトル別名
  • Mechanisms of Neuroprotective Effects of Therapeutic Acetylcholinesterase Inhibitors Used in Treatment of Alzheimer's Disease
  • アルツハイマービョウ チリョウ ニ モチイラレル アセチルコリンエステラーゼ ソガイヤク ノ シンケイ ホゴ サヨウ キジョ ニ カンスル ケンキュウ
  • Mechanisms of Neuroprotective Effects of Therapeutic Acetylcholinesterase Inhibitors Used in Treatment of Alzheimer′s Disease
  • Mechanisms of neuroprotective effect of therapeutic accetylcholinesterase inhibitors used in treatment of Alzheimer’s disease

この論文をさがす

説明

  Donepezil, galanthamine, and tacrine are therapeutic acetylcholinesterase (AChE) inhibitors used for the treatment of Alzheimer's disease. The aim of this paper is to review recent findings on their neuroprotective properties and the mechanisms of neuroprotection against glutamate neurotoxicity in rat cortical neurons. First, the hallmark of neurotoxicity induced by two different glutamate treatment conditions was examined, revealing that acute glutamate treatment (1 mM, 10 min) induces necrotic neuronal death and that moderate glutamate treatment (100 μM, 24 hr) induces apoptotic neuronal death. Next, we showed that therapeutic AChE inhibitors protect cortical neurons from glutamate neurotoxicity in a time- and concentration-dependent manner. We examined the mechanism of this neuroprotective effect and found that the neuroprotective effects against both acute and moderate glutamate treatments are mediated through nicotinic acetylcholine receptors (nAChRs), or more specifically, the effects of donepezil and galanthamine are mediated through α4- and α7-nAChR. We also showed that donepezil and galanthamine protect cortical neurons against acute glutamate treatment-induced neurotoxicity at steps before, and that tacrine protects at steps after, nitric oxide radical formation. On the other hand, the neuroprotective effects of donepezil and galanthamine, but not of tacrine, against neurotoxicity induced by moderate glutamate treatment were mediated through the phosphatidylinositol 3-kinase-Akt pathway. These findings unveiled the hitherto unknown neuroprotective effects of therapeutic AChE inhibitors and provided valuable insights into its neuroprotective mechanisms. They may very likely form the basis for a novel treatment strategy against Alzheimer's disease.<br>

収録刊行物

  • 薬学雑誌

    薬学雑誌 126 (8), 607-616, 2006

    公益社団法人 日本薬学会

被引用文献 (6)*注記

もっと見る

参考文献 (41)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ