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iPSC-Based Compound Screening and In Vitro Trials Identify a Synergistic Anti-amyloid β Combination for Alzheimer’s Disease
http://hdl.handle.net/2241/00149338
http://hdl.handle.net/2241/00149338ff30d3e5-e88c-4791-b156-b1e1cf981270
名前 / ファイル | ライセンス | アクション |
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CR_21-8.pdf (7.8 MB)
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Item type | Journal Article(1) | |||||
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公開日 | 2017-12-15 | |||||
タイトル | ||||||
タイトル | iPSC-Based Compound Screening and In Vitro Trials Identify a Synergistic Anti-amyloid β Combination for Alzheimer’s Disease | |||||
言語 | en | |||||
言語 | ||||||
言語 | eng | |||||
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 | |||||
アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
著者 |
Kondo, Takayuki
× Kondo, Takayuki× Imamura, Keiko× Funayama, Misato× Tsukita, Kayoko× Miyake, Michiyo× Ohta, Akira× Woltjen, Knut× Nakagawa, Masato× Asada, Takashi× Arai, Tetsuaki× Kawakatsu, Shinobu× Izumi, Yuishin× Kaji, Ryuji× Iwata, Nobuhisa× Inoue, Haruhisa |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | In the process of drug development, in vitro studies do not always adequately predict human-specific drug responsiveness in clinical trials. Here, we applied the advantage of human iPSC-derived neurons, which offer human-specific drug responsiveness, to screen and evaluate therapeutic candidates for Alzheimer’s disease (AD). Using AD patient neurons with nearly 100% purity from iPSCs, we established a robust and reproducible assay for amyloid β peptide (Aβ), a pathogenic molecule in AD, and screened a pharmaceutical compound library. We acquired 27 Aβ-lowering screen hits, prioritized hits by chemical structure-based clustering, and selected 6 leading compounds. Next, to maximize the anti-Aβ effect, we selected a synergistic combination of bromocriptine, cromolyn, and topiramate as an anti-Aβ cocktail. Finally, using neurons from familial and sporadic AD patients, we found that the cocktail showed a significant and potent anti-Aβ effect on patient cells. This human iPSC-based platform promises to be useful for AD drug development. | |||||
言語 | en | |||||
書誌情報 |
en : Cell Reports 巻 21, 号 8, p. 2304-2312, 発行日 2017-11 |
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ISSN | ||||||
収録物識別子タイプ | PISSN | |||||
収録物識別子 | 2211-1247 | |||||
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.celrep.2017.10.109 | |||||
PMID | ||||||
識別子タイプ | PMID | |||||
関連識別子 | 29166618 | |||||
権利情報 | ||||||
言語 | en | |||||
権利情報 | © 2017 The Author(s). | |||||
権利情報 | ||||||
言語 | en | |||||
権利情報 | This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). | |||||
出版タイプ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
出版者 | ||||||
出版者 | Cell Press | |||||
言語 | en |