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从蛋白质相互作用网络到新的治疗策略。

From protein interaction networks to novel therapeutic strategies.

机构信息

Joint IRB-BSC program in Computational Biology, Institute for Research in Biomedicine, Barcelona, Spain.

出版信息

IUBMB Life. 2012 Jun;64(6):529-37. doi: 10.1002/iub.1040. Epub 2012 May 9.

DOI:10.1002/iub.1040
PMID:22573601
Abstract

Cellular mechanisms that sustain health or contribute to disease emerge mostly from the complex interplay among various molecular entities. To understand the underlying relationships between genotype, environment and phenotype, one has to consider the intricate and nonsequential interaction patterns formed between the different sets of cellular players. Biological networks capture a variety of molecular interactions and thus provide an excellent opportunity to consider physiological characteristics of individual molecules within their cellular context. In particular, the concept of network biology and its applications contributed largely to recent advances in biomedical research. In this review, we show (i) how biological networks, i.e., protein-protein interaction networks, facilitate the understanding of pathogenic mechanisms that trigger the onset and progression of diseases and (ii) how this knowledge can be translated into effective diagnostic and therapeutic strategies. In particular, we focus on the impact of network pharmacological concepts that go beyond the classical view on individual drugs and targets aiming for combinational therapies with improved clinical efficacy and reduced safety risks.

摘要

维持健康或导致疾病的细胞机制主要源自各种分子实体之间的复杂相互作用。为了理解基因型、环境和表型之间的潜在关系,人们必须考虑不同细胞成分之间形成的复杂和非顺序的相互作用模式。生物网络捕捉了多种分子相互作用,因此为在细胞环境中考虑单个分子的生理特征提供了极好的机会。特别是,网络生物学的概念及其应用极大地促进了生物医学研究的最新进展。在这篇综述中,我们展示了(i)生物网络,即蛋白质-蛋白质相互作用网络,如何有助于理解引发疾病发生和发展的致病机制,以及(ii)如何将这些知识转化为有效的诊断和治疗策略。特别是,我们专注于网络药理学概念的影响,这些概念超越了对个体药物和靶点的传统观点,旨在通过组合治疗提高临床疗效并降低安全风险。

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