From protein interaction networks to novel therapeutic strategies

Joint IRB-BSC program in Computational Biology, Institute for Research in Biomedicine, Barcelona, Spain.
International Union of Biochemistry and Molecular Biology Life (Impact Factor: 3.14). 06/2012; 64(6):529-37. DOI: 10.1002/iub.1040
Source: PubMed


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.

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    • "Evolution of such methods has allowed the dynamic detection of PPI in living cells (Xu et al., 1999; Coulon et al., 2008; Lee et al., 2010; Quiñones et al., 2012) and nowadays in whole living organisms (Subramanian et al., 2004; Audet et al., 2010). Following this evolution scheme, PPI pathways have been deciphered and furthermore organized in higher protein networks ranging from PPI taking place in molecular complexes, to entire organelles and to whole organisms (Coulon et al., 2008; Chautard et al., 2009; Jaeger and Aloy, 2012). Our current knowledge of these PPI networks has further increased in recent years with the emerging idea that more than PPI networks themselves, the biological context in which they occur is important. "
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