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Curcumin tautomerization in the mechanism of pentameric amyloid- β42 oligomers disassembly.
http://hdl.handle.net/10422/00013575
http://hdl.handle.net/10422/000135755b579187-a230-4943-ae7b-8795c3933659
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
j.bbrc.2023.04.076 (1.7 MB)
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This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2023-06-05 | |||||
| タイトル | ||||||
| タイトル | Curcumin tautomerization in the mechanism of pentameric amyloid- β42 oligomers disassembly. | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Amyloid-β | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Oligomers | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Curcumin | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Atomic force microscopy | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Tautomerism | |||||
| 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 |
MATSUI, Atsuya
× MATSUI, Atsuya× BELLIER, Jean-Pierre× HAYASHI, Daiki× ISHIBE, Takafumi× NAKAMURA, Yoshiaki× TAGUCHI, Hiroyasu× NARUSE, Nobuyasu× MERA, Yutaka |
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| 著者別名 |
松井, 温哉
× 松井, 温哉× 林, 大貴× 田口, 弘康× 成瀬, 延康× 目良, 裕 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Alzheimer's disease is a neurologic disorder characterized by the accumulation of extracellular deposits of amyloid-β (Aβ) fibrils in the brain of patients. The key etiologic agent in Alzheimer's disease is not known; however oligomeric Aβ appears detrimental to neuronal functions and increases Aβ fibrils deposition. Previous research has shown that curcumin, a phenolic pigment of turmeric, has an effect on Aβ assemblies, although the mechanism remains unclear. In this study, we demonstrate that curcumin disassembles pentameric oligomers made from synthetic Aβ42 peptides (pentameric oAβ42), using atomic force microscopy imaging followed by Gaussian analysis. Since curcumin shows keto-enol structural isomerism (tautomerism), the effect of keto-enol tautomerism on its disassembly was investigated. We have found that curcumin derivatives capable of keto-enol tautomerization also disassemble pentameric oAβ42, while, a curcumin derivative incapable of tautomerization did not affect the integrity of pentameric oAβ42. These experimental findings indicate that keto-enol tautomerism plays an essential role in the disassembly. We propose a mechanism for oAβ42 disassembly by curcumin based on molecular dynamics calculations of the tautomerism. When curcumin and its derivatives bind to the hydrophobic regions of oAβ42, the keto-form changes predominantly to the enol-form; this transition is associated with structural (twisting, planarization and rigidification) and potential energy changes that give curcumin enough force to act as a torsion molecular-spring that eventually disassembles pentameric oAβ42. This proposed mechanism sheds new light on keto-enol tautomerism as a relevant chemical feature for designing such novel therapeutic drugs that target protein aggregation. | |||||
| 書誌情報 |
en : Biochemical and biophysical research communications 巻 666, p. 68-75, 発行日 2023-07-23 |
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| 出版者 | ||||||
| 出版者 | Elsevier B.V. | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1090-2104 | |||||
| PMID | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 37178507 | |||||
| DOI | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1016/j.bbrc.2023.04.076 | |||||
| 関連名称 | 10.1016/j.bbrc.2023.04.076 | |||||
| 権利 | ||||||
| 権利情報 | © 2023 The Authors. Published by Elsevier Inc. All rights reserved. | |||||
| フォーマット | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | application/pdf | |||||
| 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 | |||||
| 資源タイプ | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Journal Article | |||||
