| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2025-10-03 |
| タイトル |
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タイトル |
Inability of α-cyclodextrins to accommodate cholesterol potentially underlies their lack of efficacy and ototoxicity in Niemann-Pick disease type C treatment |
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言語 |
en |
| 言語 |
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|
言語 |
eng |
| キーワード |
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言語 |
en |
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キーワード |
Cholesterol |
| キーワード |
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言語 |
en |
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キーワード |
Cyclodextrin |
| キーワード |
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言語 |
en |
|
キーワード |
Intracerebroventricular administration |
| キーワード |
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言語 |
en |
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キーワード |
Molecular docking |
| キーワード |
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言語 |
en |
|
キーワード |
Niemann-Pick disease type C |
| キーワード |
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言語 |
en |
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キーワード |
Ototoxicity |
| 資源タイプ |
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資源タイプ |
journal article |
| アクセス権 |
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アクセス権 |
open access |
| 著者 |
Yamada, Yusei
Tanaka, Mayuko
Ikeda, Yusei
Kondo, Yuki
Takeo, Toru
Nakagata, Naomi
Miwa, Toru
Takeda, Hiroki
Orita, Yorihisa
Motoyama, Keiichi
Higashi, Taishi
Arima, Hidetoshi
Seki, Takahiro
Kurauchi, Yuki
Katsuki, Hiroshi
Higaki, Katsumi
Matsusaka, Kotaro
Minami, Kentaro
Yoshikawa, Naoki
池田, 龍二
WEKO
33940
e-Rad_Researcher
50398278
| ja |
池田, 龍二
宮崎大学
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| ja-Kana |
イケダ, リュウジ
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| en |
Ikeda, Ryuji
University of Miyazaki
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Search repository
Matsuo, Muneaki
Irie, Tetsumi
Ishitsuka, Yoichi
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| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Niemann-Pick disease type C (NPC) is a life-threatening neurodegenerative disease caused by impaired intracellular cholesterol trafficking. A cyclic heptasaccharide, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), is currently under clinical investigation for treating NPC, but its ototoxicity remains problematic. We previously reported that β- and γ-forms of cyclodextrin (CD) derivatives with various substituents capable of accommodating/solubilizing unesterified cholesterol (UC) exerted more pronounced therapeutic and ototoxic effects when administered intracerebroventricularly than subcutaneously for NPC treatment. However, the impact of substituent variations on these effects is unconfirmed for cyclic hexasaccharides, α-CD derivatives. Here, we investigated these effects for α-CD derivatives with various replaced substituents from the perspective of their interaction with UC. Even when administered intracerebroventricularly, a representative α-CD derivative had no impact on survival in NPC model mice. The normalization of intracellular cholesterol trafficking in NPC model cells and the auditory dysfunction in wild-type mice, both caused by HP-β-CD, were not seen for the α-CD derivatives, regardless of their substituent variations. Solubility and molecular simulation analyses showed negligible UC-solubilizing ability of α-CD derivatives because of their insufficient capacity to accommodate the UC molecule, rather than their substituent variations. These results underscore the importance of UC accommodation by CD for both efficacy and ototoxicity in NPC treatment. |
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言語 |
en |
| 書誌情報 |
en : Scientific reports
巻 15,
号 1,
p. 30857,
発行日 2025-08-22
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| 出版者 |
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出版者 |
Springer Science and Business Media LLC |
|
言語 |
en |
| ISSN |
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収録物識別子タイプ |
EISSN |
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収録物識別子 |
20452322 |
| DOI |
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関連タイプ |
isVersionOf |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1038/s41598-025-15599-0 |
| 著者版フラグ |
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出版タイプ |
VoR |
fulltext (3.4 MB)
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