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アミロイド線維形成の重合核依存性重合モデルと線維形成阻害薬の探索
http://hdl.handle.net/2297/28399
http://hdl.handle.net/2297/28399f56ffd0c-e1ce-4e7f-b470-f5a52d20baf3
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
ME-PR-ONO-K-503.pdf (891.2 kB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2017-10-03 | |||||
| タイトル | ||||||
| タイトル | アミロイド線維形成の重合核依存性重合モデルと線維形成阻害薬の探索 | |||||
| タイトル | ||||||
| タイトル | A Search for Antiamyloidogenic Compounds Based on a Nucleation-Dependent Polymerization Model | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | jpn | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| 著者 |
内木, 宏延
× 内木, 宏延× 長谷川, 一浩× 小野, 賢二郎× 山田, 正仁 |
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| 書誌情報 |
藥學雜誌 = Journal of the Pharmaceutical Society of Japan 巻 130, 号 4, p. 503-509, 発行日 2010-01-01 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0031-6903 | |||||
| NCID | ||||||
| 収録物識別子タイプ | NCID | |||||
| 収録物識別子 | AN00284903 | |||||
| DOI | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1248/yakushi.130.503 | |||||
| 出版者 | ||||||
| 出版者 | 日本薬学会 = The Pharmaceutical Society of Japan | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | We have proposed that a nucleation-dependent polymerization model could explain the general mechanisms of amyloid fibril formation in vitro. Based on this model, we systematically demonstrated that several classes of organic compounds (e.g., wine-related polyphenols, non-steroidal anti-inflammatory drugs) not only inhibit the formation of Aβ amyloid fibrils from Aβ and their extension, but also destabilize Aβ amyloid fibrils dose-dependently in vitro. We found significant positive correlations of the effective concentrations (EC50) of these compounds ranging from 10 nM to 10 μM, for the formation and destabilization of Aβ amyloid fibrils. We next investigated the anti-amyloidogenic effects of five flavonoids on Aβ amyloid fibrils in vitro. Oxidized flavonoids generally inhibited fibril formation significantly more potently than fresh compounds. By surface plasmon resonance (SPR) analysis, distinct association and dissociation reactions of myricetin (Myr) to Aβ amyloid fibrils were observed, in contrast to the very weak binding to the Aβ monomer. A significant decrease in the rate of fibril extension was observed when>0.5 μM of Myr was injected into the SPR experimental system. These findings suggest that flavonoids, especially Myr exert an anti-amyloidogenic effect in vitro by preferentially and reversibly binding to the amyloid fibril structure of fibrils, rather than to Aβ monomers. This working model should prove useful not only for the rational development of preventives and therapeutics for Alzheimers disease and other human amyloidosis, but also for understanding the basic mode of action of amyloid imaging compounds. | |||||
| 権利 | ||||||
| 権利情報 | Copyright (c) 2010 by the PHARMACEUTICAL SOCIETY OF JAPAN | |||||
| 権利URI | ||||||
| 権利情報 | http://www.pharm.or.jp/ | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| 関連URI | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | http://ci.nii.ac.jp/naid/130000259538 | |||||
| 関連URI | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://japanlinkcenter.org/JST.JSTAGE/yakushi/130.503 | |||||
