3,3',4',5'-Tetrahydroxyflavone Induces Formation of Large Aggregates of Amyloid β Protein
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- Ushikubo Hiroko
- Laboratory of Pharmacology, Faculty of Pharmacy and Research Institute of Pharmaceutical Sciences, Musashino University
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- Tanimoto Yui
- Laboratory of Pharmacology, Faculty of Pharmacy and Research Institute of Pharmaceutical Sciences, Musashino University
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- Abe Kazuho
- Laboratory of Pharmacology, Faculty of Pharmacy and Research Institute of Pharmaceutical Sciences, Musashino University
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- Asakawa Tomohiro
- Synthetic Organic & Medicinal Chemistry, School of Pharmaceutical Sciences, University of Shizuoka
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- Kan Toshiyuki
- Synthetic Organic & Medicinal Chemistry, School of Pharmaceutical Sciences, University of Shizuoka
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- Akaishi Tatsuhiro
- Laboratory of Pharmacology, Faculty of Pharmacy and Research Institute of Pharmaceutical Sciences, Musashino University
書誌事項
- タイトル別名
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- 3,3′,4′,5′-Tetrahydroxyflavone Induces Formation of Large Aggregates of Amyloid β Protein
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説明
Amyloid β protein (Aβ) self-assembles into insoluble fibrils, and forms the senile plaques associated with Alzheimer’s disease. 3,3′,4′,5′-Tetrahydroxyflavone, a synthetic analogue of the natural flavonoid fisetin, has been found to potently inhibit Aβ fibril formation. In the present study, we investigated how inhibition of Aβ fibril formation by this flavonoid affects Aβ conformation and neurotoxicity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis of Aβ1-42 (20 µM) incubated with or without 3,3′,4′,5′-tetrahydroxyflavone demonstrated that 3,3′,4′,5′-tetrahydroxyflavone (100 µM) rapidly caused formation of atypical Aβ conformers, which appeared as a very broad, smear-like band in the high molecular weight region and were distinguishable from soluble Aβ oligomers or mature Aβ fibrils. Transmission electron microscopy (TEM) revealed that large spherical Aβ aggregates were preferentially formed in the presence of 3,3′,4′,5′-tetrahydroxyflavone. The SDS-resistant, smear-like band on SDS-PAGE and the large spherical aggregates in TEM both disappeared after heat treatment (100°C, 10 min). Furthermore, a neurotoxicity assay with cultured rat hippocampal neurons demonstrated that Aβ incubated with 3,3′,4′,5′-tetrahydroxyflavone was significantly less toxic than Aβ incubated without the flavonoid. These results suggest that the newly synthesized fisetin analogue 3,3′,4′,5′-tetrahydroxyflavone directly produces atypical, large Aβ aggregates and reduces Aβ toxicity.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 37 (5), 748-754, 2014
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204632462208
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- NII論文ID
- 130004147321
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- NII書誌ID
- AA10885497
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- COI
- 1:STN:280:DC%2BC2cnpsVCltg%3D%3D
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 025419844
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- PubMed
- 24789998
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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- PubMed
- CiNii Articles
- KAKEN
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- 抄録ライセンスフラグ
- 使用不可