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Cited by 174

The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.

Anti-Aβ Drug Screening Platform Using Human iPS Cell-Derived Neurons for the Treatment of Alzheimer's Disease

Open access
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·2011·PLoS ONE

Abstract

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.

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Metadata

Authors
Yahata, N., Asai, M., Kitaoka, S., Takahashi, K., Asaka, I., Hioki, H., Kaneko, T., Maruyama, K., Saido, T. C., Nakahata, T., Asada, T., Yamanaka, S., Iwata, N., & Inoue, H.
Venue
PLoS ONE
Published
2011-09-30
Volume
6
Issue
9
Pages
e25788
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2105151327
Cited by
174
References
17
FWCI
11.56
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: Anti-Aβ Drug Screening Platform Using Human iPS Cell-Derived Neurons for the Treatment of Alzheimer's Disease. https://app.cochat.ai/papers/10.1371/journal.pone.0025788
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Yahata, N., Asai, M., Kitaoka, S., Takahashi, K., Asaka, I., Hioki, H., Kaneko, T., Maruyama, K., Saido, T. C., Nakahata, T., Asada, T., Yamanaka, S., Iwata, N., & Inoue, H. (2011). Anti-Aβ Drug Screening Platform Using Human iPS Cell-Derived Neurons for the Treatment of Alzheimer's Disease. PLoS ONE. https://doi.org/10.1371/journal.pone.0025788

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