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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/2241/00149338
ff30d3e5-e88c-4791-b156-b1e1cf981270
名前 / ファイル ライセンス アクション
CR_21-8.pdf CR_21-8.pdf (7.8 MB)
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Item type アイテムタイプJ(1)
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
言語 eng
資源タイプ
資源タイプ journal article
著者 Kondo Takayuki

× Kondo Takayuki

en Kondo Takayuki

Imamura Keiko

× Imamura Keiko

en Imamura Keiko

Funayama Misato

× Funayama Misato

en Funayama Misato

Tsukita Kayoko

× Tsukita Kayoko

en Tsukita Kayoko

Miyake Michiyo

× Miyake Michiyo

en Miyake Michiyo

Ohta Akira

× Ohta Akira

en Ohta Akira

Woltjen Knut

× Woltjen Knut

en Woltjen Knut

Nakagawa Masato

× Nakagawa Masato

en Nakagawa Masato

Asada Takashi

× Asada Takashi

en Asada Takashi

Arai Tetsuaki

× Arai Tetsuaki

en Arai Tetsuaki

Kawakatsu Shinobu

× Kawakatsu Shinobu

en Kawakatsu Shinobu

Izumi Yuishin

× Izumi Yuishin

en Izumi Yuishin

Kaji Ryuji

× Kaji Ryuji

en Kaji Ryuji

Iwata Nobuhisa

× Iwata Nobuhisa

en Iwata Nobuhisa

Inoue Haruhisa

× Inoue Haruhisa

en Inoue Haruhisa

抄録
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.
書誌情報 en : Cell Reports

巻 21, 号 8, p. 2304-2312, 発行日 2017-11
PISSN
収録物識別子 2211-1247
アクセス権
アクセス権 open access
権利情報
権利情報 © 2017 The Author(s).
権利情報
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/).
出版者
出版者 Cell Press
出版タイプ
出版タイプ VoR
DOI
関連タイプ isIdenticalTo
関連識別子 https://doi.org/10.1016/j.celrep.2017.10.109
PMID
関連識別子 29166618
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