A systematic strategy for discovering a therapeutic drug for Alzheimer's disease and its target molecule

Zhiyou Yang, Tomoharu Kuboyama, Chihiro Tohda*

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

81 被引用数 (Scopus)

抄録

Natural medicines are attractive sources of leading compounds that can be used as interventions for neurodegenerative disorders. The complexity of their chemical components and undetermined bio-metabolism have greatly hindered both the use of natural medicines and the identification of their active constituents. Here, we report a systematic strategy for evaluating the bioactive candidates in natural medicines used for Alzheimer's disease (AD). We found that Drynaria Rhizome could enhance memory function and ameliorate AD pathologies in 5XFAD mice. Biochemical analysis led to the identification of the bio-effective metabolites that are transferred to the brain, namely, naringenin and its glucuronides. To explore the mechanism of action, we combined the drug affinity responsive target stability with immunoprecipitation-liquid chromatography/mass spectrometry analysis, identifying the collapsin response mediator protein 2 protein as a target of naringenin. Our study indicates that biochemical analysis coupled with pharmacological methods can be used in the search for new targets for AD intervention.

本文言語英語
論文番号340
ジャーナルFrontiers in Pharmacology
8
JUN
DOI
出版ステータス出版済み - 2017

ASJC Scopus 主題領域

  • 薬理学
  • 薬理学(医学)

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