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癫痫与共病抑郁双重管理的战略途径分析:系统生物学视角

Strategic pathway analysis for dual management of epilepsy and comorbid depression: a systems biology perspective.

作者信息

Kaur Arvinder, Verma Varinder, Goel Rajesh Kumar

机构信息

Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab India 147002.

出版信息

In Silico Pharmacol. 2024 Apr 30;12(1):36. doi: 10.1007/s40203-024-00208-1. eCollection 2024.

Abstract

UNLABELLED

Depression is a common psychiatric comorbidity among patients with epilepsy (PWE), affecting more than a third of PWE. Management of depression may improve quality of life of epileptic patients. Unfortunately, available antidepressants worsen epilepsy by reducing the seizure threshold. This situation demands search of new safer target for combined directorate of epilepsy and comorbid depression. A system biology approach may be useful to find novel pathways/markers for the cure of both epilepsy and associated depression via analyzing available genomic and proteomic information. Hence, the system biology approach using curated 64 seed genes involved in temporal lobe epilepsy and mental depression was applied. The interplay of 600 potential proteins was revealed by the Disease Module Detection (DIAMOnD) Algorithm for the treatment of both epilepsy and comorbid depression using these seed genes. The gene enrichment analysis of seed and diamond genes through DAVID suggested 95 pathways. Selected pathways were refined based on their syn or anti role in epilepsy and depression. In conclusion, total 8 pathways and 27 DIAMOnD genes/proteins were finally deduced as potential new targets for modulation of selected pathways to manage epilepsy and comorbid depression.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s40203-024-00208-1.

摘要

未标注

抑郁症是癫痫患者(PWE)中常见的精神共病,影响超过三分之一的PWE。抑郁症的治疗可能会改善癫痫患者的生活质量。不幸的是,现有的抗抑郁药会降低癫痫发作阈值,从而使癫痫病情恶化。这种情况需要为癫痫和共病抑郁症的联合治疗寻找新的更安全的靶点。系统生物学方法可能有助于通过分析现有的基因组和蛋白质组信息,找到治疗癫痫和相关抑郁症的新途径/标志物。因此,应用了使用策划的64个参与颞叶癫痫和精神抑郁症的种子基因的系统生物学方法。通过疾病模块检测(DIAMOnD)算法揭示了600种潜在蛋白质之间的相互作用,以使用这些种子基因治疗癫痫和共病抑郁症。通过DAVID对种子基因和DIAMOnD基因进行基因富集分析,发现了95条途径。根据它们在癫痫和抑郁症中的协同或拮抗作用对选定的途径进行了优化。总之,最终推断出总共8条途径和27个DIAMOnD基因/蛋白质作为调节选定途径以治疗癫痫和共病抑郁症的潜在新靶点。

补充信息

在线版本包含可在10.1007/s40203-024-00208-1获取的补充材料。

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本文引用的文献

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The Possible Role of Brain-derived Neurotrophic Factor in Epilepsy.脑源性神经营养因子在癫痫中的可能作用。
Neurochem Res. 2024 Mar;49(3):533-547. doi: 10.1007/s11064-023-04064-x. Epub 2023 Nov 25.
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Neuroinflammatory mediators in acquired epilepsy: an update.获得性癫痫中的神经炎症介质:更新。
Inflamm Res. 2023 Apr;72(4):683-701. doi: 10.1007/s00011-023-01700-8. Epub 2023 Feb 6.
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The JAK-STAT Signaling Pathway in Epilepsy.癫痫中的 JAK-STAT 信号通路。
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Role of HMGB1/TLR4 and IL-1β/IL-1R1 Signaling Pathways in Epilepsy.HMGB1/TLR4和IL-1β/IL-1R1信号通路在癫痫中的作用
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Neuroinflammation and Proinflammatory Cytokines in Epileptogenesis.神经炎症和促炎细胞因子在癫痫发生中的作用。
Mol Neurobiol. 2022 Mar;59(3):1724-1743. doi: 10.1007/s12035-022-02725-6. Epub 2022 Jan 11.
9
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