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Anti-Aβ Drug Screening Platform Using Human iPS Cell-Derived Neurons for the Treatment of Alzheimer's Disease
http://hdl.handle.net/10069/26003
http://hdl.handle.net/10069/26003fd3e4486-1cc4-43df-95ee-c1874c204b95
名前 / ファイル | ライセンス | アクション |
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journal.pone.0025788.pdf (1.3 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2011-10-11 | |||||
タイトル | ||||||
タイトル | Anti-Aβ Drug Screening Platform Using Human iPS Cell-Derived Neurons for the Treatment of Alzheimer's Disease | |||||
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 | |||||
著者 |
Yahata, Naoki
× Yahata, Naoki× Asai, Masashi× Kitaoka, Shiho× Takahashi, Kazutoshi× Asaka, Isao× Hioki, Hiroyuki× Kaneko, Takeshi× Maruyama, Kei× Saido, Takaomi C.× Nakahata, Tatsutoshi× Asada, Takashi× Yamanaka, Shinya× Iwata, Nobuhisa× Inoue, Haruhisa |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Background:Alzheimer's disease (AD) is a neurodegenerative disorder that causes progressive memory and cognitive decline during middle to late adult life. The AD brain is characterized by deposition of amyloid β peptide (Aβ), which is produced from amyloid precursor protein by β- and γ-secretase (presenilin complex)-mediated sequential cleavage. Induced pluripotent stem (iPS) cells potentially provide an opportunity to generate a human cell-based model of AD that would be crucial for drug discovery as well as for investigating mechanisms of the disease. Methodology/Principal Findings:We differentiated human iPS (hiPS) cells into neuronal cells expressing the forebrain marker, Foxg1, and the neocortical markers, Cux1, Satb2, Ctip2, and Tbr1. The iPS cell-derived neuronal cells also expressed amyloid precursor protein, β-secretase, and γ-secretase components, and were capable of secreting Aβ into the conditioned media. Aβ production was inhibited by β-secretase inhibitor, γ-secretase inhibitor (GSI), and an NSAID; however, there were different susceptibilities to all three drugs between early and late differentiation stages. At the early differentiation stage, GSI treatment caused a fast increase at lower dose (Aβ surge) and drastic decline of Aβ production. Conclusions/Significance:These results indicate that the hiPS cell-derived neuronal cells express functional β- and γ-secretases involved in Aβ production; however, anti-Aβ drug screening using these hiPS cell-derived neuronal cells requires sufficient neuronal differentiation. | |||||
書誌情報 |
PLoS ONE 巻 6, 号 9, p. e25788, 発行日 2011-09-30 |
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出版者 | ||||||
出版者 | PLoS ONE | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1371/journal.pone.0025788 | |||||
権利 | ||||||
権利情報 | © 2011 Yahata et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | |||||
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 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | PLoS ONE, 6(9), e25788; 2011 |