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神经递质信号通路的布尔网络分析

Boolean network analysis of a neurotransmitter signaling pathway.

作者信息

Gupta Simone, Bisht Siddharth S, Kukreti Ritushree, Jain Sanjeev, Brahmachari Samir K

机构信息

Institute of Genomics and Integrative Biology, CSIR, Delhi 110007, India.

出版信息

J Theor Biol. 2007 Feb 7;244(3):463-9. doi: 10.1016/j.jtbi.2006.08.014. Epub 2006 Aug 26.

Abstract

BACKGROUND

A Boolean network is a simple computational model that may provide insight into the overall behavior of genetic networks and is represented by variables with two possible states (on/off), of the individual nodes/genes of the network. In this study, a Boolean network model has been used to simulate a molecular pathway between two neurotransmitter receptor, dopamine and glutamate receptor, systems in order to understand the consequence of using logic gate rules between nodes, which have two possible states (active and inactive).

RESULTS

The dynamical properties of this Boolean network model of the biochemical pathway shows that, the pathway is stable and that, deletion/knockout of certain biologically important nodes cause significant perturbation to this network. The analysis clearly shows that in addition to the expected components dopamine and dopamine receptor 2 (DRD2), Ca(2+) ions play a critical role in maintaining stability of the pathway.

CONCLUSION

So this method may be useful for the identification of potential genetic targets, whose loss of function in biochemical pathways may be responsible for disease onset. The molecular pathway considered in this study has been implicated with a complex disorder like schizophrenia, which has a complex multifactorial etiology.

摘要

背景

布尔网络是一种简单的计算模型,它可以为基因网络的整体行为提供见解,并由网络中各个节点/基因的具有两种可能状态(开/关)的变量表示。在本研究中,布尔网络模型已被用于模拟两种神经递质受体(多巴胺和谷氨酸受体)系统之间的分子途径,以便了解在具有两种可能状态(激活和失活)的节点之间使用逻辑门规则的结果。

结果

该生化途径布尔网络模型的动力学特性表明,该途径是稳定的,并且删除/敲除某些生物学上重要的节点会对该网络造成重大扰动。分析清楚地表明,除了预期的成分多巴胺和多巴胺受体2(DRD2)外,钙离子在维持途径的稳定性方面起着关键作用。

结论

因此,这种方法可能有助于识别潜在的基因靶点,其在生化途径中的功能丧失可能是疾病发作的原因。本研究中考虑的分子途径与精神分裂症等复杂疾病有关,精神分裂症具有复杂的多因素病因。

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