薬理学的標的としてのシグナリングのダイナミクス
Marcelo Behar1, Derren Barken, Shannon L Werner
1Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA; San Diego Center for Systems Biology, University of California, San Diego, La Jolla, CA 92093, USA; Computational Biosciences Institute, University of California, Los Angeles, Los Angeles, CA 90025, USA; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90025, USA.
Cell
|October 15, 2013
まとめ
疾患における複雑なシグナル伝達経路をターゲットにすることは,その広範な効果のために困難です. この研究は,ハブだけでなく,ダイナミックシグナルコードをターゲットにすることで,治療特異性を達成できることを明らかにしています.
科学分野:
- 細胞信号のダイナミクス
- 薬理学的ターゲティング
- システム生物学 システム生物学
背景:
- ネットワーク化されたシグナリングハブは,様々な病気に関与しています.
- これらのハブの薬理学的阻害は,機能的プレオトロピー (複数の効果) のためにしばしば失敗します.
- 既存の戦略には,治療特異性が欠けている.
研究 の 目的:
- ダイナミック・シグナリング特性が,薬理学的に治療特異性をターゲットにできるかどうかを調査する.
- 信号ハブの刺激特異的阻害の原則を特定する.
- 信号ダイナミクスをターゲティングする可能性を実証する.
主な方法:
- 信号ハブトポロジーとダイナミック信号プロファイルの仮想スクリーニング.
- 信号ダイナミクスの数学分析.
- NFκBシグナリングモジュールを用いた実験的検証.
主要な成果:
- 選択的阻害に適したシグナルハブトポロジーとダイナミックプロファイルの組み合わせを特定しました.
- 刺激特異的抑制のための数学的原理を明らかにした.
- サイトカインまたは病原体成分に対するNFκB反応の選択的阻害が実証されています.
結論:
- 信号ダイナミクスは,有効な薬理学的標的を代表する.
- プレオトロプシグナリングハブの刺激特異的な治療法を開発するための原則が定められた.
- このアプローチは,より正確な疾患治療への道を開きます.
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