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Fine-tuned cholesterol solubilizer, mono-6-O-α-D-maltosyl-γ-cyclodextrin, ameliorates experimental Niemann-Pick disease type C without hearing loss.
http://hdl.handle.net/10458/00010420
http://hdl.handle.net/10458/000104207e335d6d-2d7f-45d7-ba32-0d74891440a0
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
本文 (8.8 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2022-10-17 | |||||
| タイトル | ||||||
| タイトル | Fine-tuned cholesterol solubilizer, mono-6-O-α-D-maltosyl-γ-cyclodextrin, ameliorates experimental Niemann-Pick disease type C without hearing loss. | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| キーワード | Cholesterol | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| キーワード | Cyclodextrin | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| キーワード | Niemann–Pick disease type C | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| キーワード | Ototoxicity | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| キーワード | Physicochemical property | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| キーワード | Solubilization | |||||
| 資源タイプ | ||||||
| 資源タイプ | journal article | |||||
| 著者 |
山田, 侑世
× 山田, 侑世× 南, 謙太朗× 吉川, 直樹× 池田, 龍二× Yamada, Yusei× Miwa, Toru× Nakashima, Masaki× Shirakawa, Aina× Ishii, Akira× Namba, Nanami× Kondo, Yuki× Takeo, Toru× Nakagata, Naomi× Motoyama, Keiichi× Higashi, Taishi× Arima, Hidetoshi× Kurauchi, Yuki× Seki, Takahiro× Katsuki, Hiroshi× Okada, Yasuyo× Ichikawa, Atsushi× Higaki, Katsumi× Hayashi, Ken× Minami, Kentaro× Yoshikawa, Naoki× Ikeda, Ryuji× Ishikawa, Yoshihide× Kajii, Tomohito× Tachii, Kyoko× Takeda, Hiroki× Orita, Yorihisa× Matsuo, Muneaki× Irie, Tetsumi× Ishitsuka, Yoichi |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Niemann-Pick disease type C （NPC） is a fatal disorder with abnormal intracellular cholesterol trafficking resulting in neurodegeneration and hepatosplenomegaly. A cyclic heptasaccharide with different degrees of substitution of 2-hydroxypropyl groups, 2-hydroxypropyl-β-cyclodextrin （HP-β-CD）, acts as a strong cholesterol solubilizer and is under investigation for treating this disease in clinical trials, but its physicochemical properties and ototoxicity remain a concern. Here, we evaluated the potential of mono-6-O-α-maltosyl-γ-CD （G2-γ-CD）, a single-maltose-branched cyclic octasaccharide with a larger cavity than HP-β-CD, for treating NPC. We identified that G2-γ-CD ameliorated NPC manifestations in model mice and showed lower ototoxicity in mice than HP-β-CD. To investigate the molecular mechanisms of action behind the differential ototoxicity of these CDs, we performed cholesterol solubility analysis, proton nuclear magnetic resonance spectroscopy, and molecular modeling, and estimated that the cholesterol inclusion mode of G2-γ-CD maintained solely the 1:1 inclusion complex, whereas that of HP-β-CD shifted to the highly-soluble 2:1 complex at higher concentrations. We predicted the associations of these differential complexations of CDs with cholesterol with the profile of disease attenuation and of the auditory cell toxicity using specific cell models. We proposed that G2-γ-CD can serve as a fine-tuned cholesterol solubilizer for treating NPC, being highly biocompatible and physicochemically suitable for clinical application. | |||||
| 書誌情報 |
Biomedicine & pharmacotherapy 巻 155, p. 113698, 発行日 2022-09-16 |
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| 出版者 | ||||||
| 出版者 | Elsevier | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1950-6007 | |||||
| PubMed番号 | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 36116252 | |||||
| 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.biopha.2022.113698 | |||||
| 権利 | ||||||
| 権利情報 | © 2022 The Authors. Published by Elsevier Masson SAS. | |||||
| 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 | |||||
