A systems level analysis of epileptogenesis-associated proteome alterations
A systems level analysis of epileptogenesis-associated proteome alterations
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DOI：
10.1016/j.nbd.2017.05.017
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发表时间：
2017-09-01
影响因子：
6.1
通讯作者：
Potschka, Heidrun
中科院分区：
文献类型：
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作者：
Keck, Michael;Fournier, Anna;Potschka, Heidrun
尽管进行了大量的研究工作，但关于癫痫发生和癫痫机制的知识仍然被认为是不完整和有限的。然而，深入了解分子病理生理过程是合理选择创新的生物标志物和目标candides.There的关键，我们从不同阶段的慢性大鼠癫痫模型的蛋白质组数据进行全面的系统水平的分析。加权基因共表达网络分析确定了几个模块的相互联系的蛋白质组，反映不同的分子方面的癫痫在海马和海马旁皮质。这些模块的表征不仅进一步验证了数据，而且还揭示了以前在癫痫发展背景下未描述的分子过程的调节。这些数据集还提供了有关时间模式的有价值的信息，特别是当涉及到多靶点网络药理学方法时，应该考虑到预防策略的发展。此外，主成分分析提出了候选生物标志物，这可能会为旨在预测不同阶段癫痫发生或确认癫痫表现的新型分子成像方法的设计提供信息。进一步的研究是必要的，以区分分子的变化，这与癫痫发生与那些反映了癫痫持续状态的后果。(C)2017作者爱思唯尔公司出版
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.