A systems level analysis of epileptogenesis-associated proteome alterations

NEUROBIOLOGY OF DISEASE

卷:105

Article

Keck, Michael¹  Androsova, Ganna²  Gualtieri, Fabio¹  Walker, Andreas¹  von Rueden, Eva-Lotta¹  Russmann, Vera¹  Deeg, Cornelia A.^3,4  Hauck, Stefanie M.⁵  Krause, Roland²  Potschka, Heidrun¹ 

[1] LMU, Inst Pharmacol Toxicol & Pharm, Koeniginstr 16, D-80539 Munich, Germany

[2] Univ Luxembourg, LCSB, Bioinformat Core, 6 Ave Swing, L-4367 Belvaux, Luxembourg

[3] LMU, Dept Vet Sci, Inst Anim Physiol, D-80539 Munich, Germany

[4] Philipps Univ Marburg, Expt Ophthalmol, D-35037 Marburg, Germany

[5] Helmholtz Ctr Munich, Res Unit Prot Sci, D-85764 Neuherberg, Germany

关键词: Status epilepticus;    WGCNA;    Epilepsy;    Network;    Mass spectrometry;    Bioinformatics;    Proteome;   

DOI  :  10.1016/j.nbd.2017.05.017

来源: Elsevier

【 摘 要 】

Despite intense research efforts, the knowledge about the mechanisms of epileptogenesis and epilepsy is still considered incomplete and limited. However, an in-depth understanding of molecular pathophysiological processes is crucial for the rational selection of innovative biomarkers and target candidates. Here, we subjected proteomic data from different phases of a chronic rat epileptogenesis model to a comprehensive systems level analysis. Weighted Gene Co-expression Network analysis identified several modules of interconnected protein groups reflecting distinct molecular aspects of epileptogenesis in the hippocampus and the parahippocampal cortex. Characterization of these modules did not only further validate the data but also revealed regulation of molecular processes not described previously in the context of epilepsy development. The data sets also provide valuable information about temporal patterns, which should be taken into account for development of preventive strategies in particular when it comes to multi-targeting network pharmacology approaches. In addition, principal component analysis suggests candidate biomarkers, which might inform the design of novel molecular imaging approaches aiming to predict epileptogenesis during different phases or confirm epilepsy manifestation. Further studies are necessary to distinguish between molecular alterations, which correlate with epileptogenesis versus those reflecting a mere consequence of the status epilepticus. (C) 2017 The Authors. Published by Elsevier Inc.

【 授权许可】

Free