Scholarlink

<p>In early drug discovery, in vitro screening is frequently used, but selected candidates often fail in vivo. Induced pluripotent stem cell (iPSC)–based disease models offer improved physiological relevance; however, the high costs of media and differentiation procedures limit large-scale testing. Here, we develop a high-throughput conditioned-media-based screening system—the High-throughput screening technology for Aggregation Inhibitors of Diseased cell-derived Aggregative Proteins (HaiDap) system—to identify inhibitors of aggregation induced by iPSC-secreted amyloid β (Aβ). Using conditioned media derived from differentiated iPSCs of a male Alzheimer’s disease patient, we screen extracts from 22 edible plants. Whereas PBS-based assays showed 40.9% (9/22) apparent selectivity, the HaiDap system demonstrates higher specificity (13.6%; 3/22). All three identified extracts (<i>O. aristatus</i>, <i>S. aromaticum</i>, and <i>G. yesoense</i>) significantly delay Aβ aggregation on neuronal surfaces in an iPSC-based assay. These findings suggest that the HaiDap system enables efficient, accurate, and low-cost screening of amyloid aggregation inhibitors.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

A high-throughput conditioned-media-based screening system identifies inhibitors of aggregation induced by iPSC-secreted amyloid β

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月24日

查看全文
  • Masahiro Kuragano,
  • Naoki Nishishita,
  • Koki Araya,
  • Akira Kobayashi,
  • Taro Q. P. Noguchi,
  • Kenichi Watanabe,
  • Shinya Watanabe,
  • Stefan Baar,
  • Koji Uwai,
  • Kiyotaka Tokuraku

摘要

In early drug discovery, in vitro screening is frequently used, but selected candidates often fail in vivo. Induced pluripotent stem cell (iPSC)–based disease models offer improved physiological relevance; however, the high costs of media and differentiation procedures limit large-scale testing. Here, we develop a high-throughput conditioned-media-based screening system—the High-throughput screening technology for Aggregation Inhibitors of Diseased cell-derived Aggregative Proteins (HaiDap) system—to identify inhibitors of aggregation induced by iPSC-secreted amyloid β (Aβ). Using conditioned media derived from differentiated iPSCs of a male Alzheimer’s disease patient, we screen extracts from 22 edible plants. Whereas PBS-based assays showed 40.9% (9/22) apparent selectivity, the HaiDap system demonstrates higher specificity (13.6%; 3/22). All three identified extracts (O. aristatus, S. aromaticum, and G. yesoense) significantly delay Aβ aggregation on neuronal surfaces in an iPSC-based assay. These findings suggest that the HaiDap system enables efficient, accurate, and low-cost screening of amyloid aggregation inhibitors.