World Scientific
  • Search
  •   
Skip main navigation

Cookies Notification

We use cookies on this site to enhance your user experience. By continuing to browse the site, you consent to the use of our cookies. Learn More
×

Identification of potential drug targets for treatment of refractory epilepsy using network pharmacology

    https://doi.org/10.1142/S0219720018400024Cited by:11 (Source: Crossref)

    Epilepsy is the fourth most common neurological disease after migraine, stroke, and Alzheimer’s disease. Approximately one-third of all epilepsy cases are refractory to the existing anticonvulsants. Thus, there is an unmet need for newer antiepileptic drugs (AEDs) to manage refractory epilepsy (RE). Discovery of novel AEDs for the treatment of RE further retards for want of potential pharmacological targets, unavailable due to unclear etiology of this disease. In this regard, network pharmacology as an area of bioinformatics is gaining popularity. It combines the methods of network biology and polypharmacology, which makes it a promising approach for finding new molecular targets. This work is aimed at discovering new pharmacological targets for the treatment of RE using network pharmacology methods. In the framework of our study, the genes associated with the development of RE were selected based on analysis of available data. The methods of network pharmacology were used to select 83 potential pharmacological targets linked to the selected genes. Then, 10 most promising targets were chosen based on analysis of published data. All selected target proteins participate in biological processes, which are considered to play a key role in the development of RE. For 9 of 10 selected targets, the potential associations with different kinds of epilepsy have been recently mentioned in the literature published, which gives additional evidence that the approach applied is rather promising.

    References

    • 1. Hopkins AL, Network pharmacology: The next paradigm in drug discovery, Nat Chem Biol 4 :682–690, 2008. Crossref, MedlineGoogle Scholar
    • 2. Koborova ON, Filimonov DA, Zakharov AV et al., In silico method for identification of promising anticancer drug targets, SAR QSAR Environ Res 20 :755–766, 2009. Crossref, MedlineGoogle Scholar
    • 3. Ghiassian SD, Menche J, Barabasi AL, A DIseAse MOdule Detection (DIAMOnD) algorithm derived from a systematic analysis of connectivity patterns of disease proteins in the human interactome, PLoS Comput Biol 11 :e1004120, 2015. Crossref, MedlineGoogle Scholar
    • 4. Silberberg Y, Kupiec M, Sharan R, GLADIATOR: A global approach for elucidating disease modules, Genome Med 9 :48, 2017. Crossref, MedlineGoogle Scholar
    • 5. Irurzun-Arana I, Pastor JM, Troconiz IF et al., Advanced Boolean modeling of biological networks applied to systems pharmacology, Bioinformatics 33 :1040–1048, 2017. Crossref, MedlineGoogle Scholar
    • 6. Hsin KY, Matsuoka Y, Asai Y et al., SystemsDock: A web server for network pharmacology-based prediction and analysis, Nucleic Acids Res 44: W507–W513, 2016. Crossref, MedlineGoogle Scholar
    • 7. Hirtz D, Thurman DJ, Gwinn-Hardy K et al., How common are the “common” neurologic disorders? Neurology 68 :326–337, 2007. Crossref, MedlineGoogle Scholar
    • 8. Fisher RS, Acevedo C, Arzimanoglou A et al., ILAE official report: A practical clinical definition of epilepsy, Epilepsia 55 :475–482, 2014. Crossref, MedlineGoogle Scholar
    • 9. Kwan P, Sander JW, The natural history of epilepsy: An epidemiological view, J Neurol Neurosurg Psychiatr 75 :1376–1381, 2004. Crossref, MedlineGoogle Scholar
    • 10. Viteva E, Basic cellular and molecular mechanisms of refractory epilepsy: A review of current hypotheses, Mol Cell Epilepsy 1 :e17, 2014. Google Scholar
    • 11. Dalic L, Cook MJ, Managing drug-resistant epilepsy: Challenges and solutions, Neuropsych Dis Treat 12 :2605–2616, 2016. Crossref, MedlineGoogle Scholar
    • 12. Remy S, Gabriel S, Urban BW et al., A novel mechanism underlying drug resistance in chronic epilepsy, Ann Neurol 53 :469–479, 2003. Crossref, MedlineGoogle Scholar
    • 13. Chu H, Sun P, Yin J et al., Integrated network analysis reveals potentially novel molecular mechanisms and therapeutic targets of refractory epilepsies, PLoS One 12 :e0174964, 2017. Crossref, MedlineGoogle Scholar
    • 14. Chu H, Zhou X, Liu G et al., Network-based detection of disease modules and potential drug targets in intractable epilepsy, 8th Int Conf Systems Biology (ISB), pp. 132–140, 2014. Google Scholar
    • 15. Gebicke-Haerter PJ, Systems psychopharmacology: A network approach to developing novel therapies, World J Psychiatr 6 :66–83, 2016. Crossref, MedlineGoogle Scholar
    • 16. Zhang Y, Gao B, Xiong Y et al., Expression of SHANK3 in the temporal neocortex of patients with intractable temporal epilepsy and epilepsy rat models, Cell Mol Neurobiol 37 :857–867, 2017. Crossref, MedlineGoogle Scholar
    • 17. Hardies K, Cai Y, Jardel C et al., Loss of SYNJ1 dual phosphatase activity leads to early onset refractory seizures and progressive neurological decline, Brain 139 :2420–2430, 2016. Crossref, MedlineGoogle Scholar
    • 18. Hammer MF, Wagnon JL, Mefford HC, SCN8A-related epilepsy with encephalopathy, GeneReviews 2016. Google Scholar
    • 19. Lim JS, Kim WI, Kang HC et al., Brain somatic mutations in MTOR cause focal cortical dysplasia type II leading to intractable epilepsy, Nat Med 21 :395–400, 2015. Crossref, MedlineGoogle Scholar
    • 20. Chi X, Huang C, Li R et al., Inhibition of mTOR pathway by rapamycin decreases P-glycoprotein expression and spontaneous seizures in pharmacoresistant epilepsy, J Mol Neurosci 61 :553–562, 2017. Crossref, MedlineGoogle Scholar
    • 21. Cui L, Tao H, Wang Y et al., A functional polymorphism of the microRNA-146a gene is associated with susceptibility to drug-resistant epilepsy and seizures frequency, Seizure 27 :60–65, 2015. Crossref, MedlineGoogle Scholar
    • 22. Skalski D, Wendorff J, Romanowicz H et al., Associations between MDR1 C3435T polymorphism and drug-resistant epilepsy in the Polish population, Acta Neurol Belgica 117 :153–158, 2017. Crossref, MedlineGoogle Scholar
    • 23. Elsaadany L, El-Said M, Ali R et al., W44X mutation in the WWOX gene causes intractable seizures and developmental delay: A case report, BMC Med Genet 17 :53, 2016. Crossref, MedlineGoogle Scholar
    • 24. Lopez-Garcia MA, Feria-Romero IA, Serrano H et al., Influence of genetic variants of CYP2D6, CYP2C9, CYP2C19 and CYP3A4 on antiepileptic drug metabolism in pediatric patients with refractory epilepsy, Pharmacol Rep 69 :504–511, 2017. Crossref, MedlineGoogle Scholar
    • 25. Banerjee DA, Sharma D, Srivastava A et al., Upregulation of breast cancer resistance protein and major vault protein in drug-resistant epilepsy, Seizure 47 :9–12, 2017. Crossref, MedlineGoogle Scholar
    • 26. Beamer E, Fischer W, Engel T, The ATP-gated P2X7 receptor as a target for the treatment of drug-resistant epilepsy, Front Neurosci 11 :21, 2017. Crossref, MedlineGoogle Scholar
    • 27. McCallum AP, Gallek MJ, Ramey W et al., Cortical gene expression correlates of temporal lobe epileptogenicity, Pathophysiology 23 :181–190, 2016. Crossref, MedlineGoogle Scholar
    • 28. Noebels JL, Avoli M, Rogawski MA, Olsen RW and Delgado-Escueta AV (eds.), Jasper’s Basic Mechanisms of the Epilepsies, Bethesda MD, USA, 2012. CrossrefGoogle Scholar
    • 29. Lagunin A, Stepanchikova A, Filimonov D et al., PASS: Prediction of activity spectra for biologically active substances, Bioinformatics 16 :747–748, 2000. Crossref, MedlineGoogle Scholar
    • 30. Filimonov DA, Lagunin AA, Gloriozova TA et al., Prediction of the biological activity spectra of organic compounds using the PASS online web resource, Chem Heterocyclic Compd 50 :444–457, 2014. CrossrefGoogle Scholar
    • 31. Rozantsev GG, Frolovskii VA, Studnev NYu, New principle of search for compounds possessing anticonvulsive properties, Pharmaceut Chem J 32 :345–351, 1997. CrossrefGoogle Scholar
    • 32. Mishra A, Punia JK, Bladen C et al., Anticonvulsant mechanisms of piperine, a piperidine alkaloid, Channels (Austin) 9 :317–323, 2015. Crossref, MedlineGoogle Scholar
    • 33. Patel HM, Noolvi MN, Shirkhedkar AA et al., Anti-convulsant potential of quinazolinones, RSC Adv 6 :44435–44455, 2016. CrossrefGoogle Scholar
    • 34. Sirakanyan SN, Geronikaki A, Spinelli D et al., Pyridofuropyrrolo[1,2-a]pyrimidines and pyridofuropyrimido[1,2-a]azepines: New chemical entities (NCE) with anticonvulsive and psychotropic properties, RSC Adv 6 :49028–49038, 2016. CrossrefGoogle Scholar
    • 35. Zadorozhnii PV, Kiselev VV, Pokotylo IO et al., In silico prediction of anticonvulsant activity of N-(2,2,2-trichloro-1-hydroxyethyl) alkylcarboxamides, J Chem Pharmaceut Sci 10, 1099–1105, 2017. Google Scholar
    • 36. Pogodin PV, Lagunin AA, Filimonov DA et al., PASS targets: Ligand-based multi-target computational system based on a public data and naïve Bayes approach, SAR QSAR Environ Res 26 :783–793, 2015. Crossref, MedlineGoogle Scholar
    • 37. Odell LR, Abdel-Hamid MK, Hill TA et al., Pyrimidine-based inhibitors of dynamin I GTPase activity: Competitive inhibition at the Pleckstrin homology domain, J Med Chem 60 :349–361, 2017. Crossref, MedlineGoogle Scholar
    • 38. Muegge I, Mukherjee P, An overview of molecular fingerprint similarity search in virtual screening, Exp Opin Drug Discov 11 :137–148, 2016. Crossref, MedlineGoogle Scholar
    • 39. Kitchen DB, Decornez H, Furr JR, Bajorath J, Docking and scoring in virtual screening for drug discovery: Methods and applications, Nat Rev Drug Discov 3 :935–949, 2004. Crossref, MedlineGoogle Scholar
    • 40. Lemke JR, Hendrickx R, Geider K et al., GRIN2B mutations in West syndrome and intellectual disability with focal epilepsy, Ann Neurol 75 :147–154, 2014. Crossref, MedlineGoogle Scholar
    • 41. Perosa SR, Arganaraz GA, Goto EM et al., Kinin B1 and B2 receptors are overexpressed in the hippocampus of humans with temporal lobe epilepsy, Hippocampus 17 :26–33, 2007. Crossref, MedlineGoogle Scholar
    • 42. Das A, Balan S, Banerjee M et al., Drug resistance in epilepsy and the ABCB1 gene: The clinical perspective, Ind J Human Genet 17 :S12–S21, 2011. Crossref, MedlineGoogle Scholar
    • 43. Sayitoglu MA, Sema S, Unlucerci Y et al., Neuronal Nos (Nos1) polymorphism in patients with epilepsy: A pilot study, J Neurolog Sci 23 :20–25, 2006. Google Scholar
    • 44. De Fusco M, Vago R, Striano P et al., The α2B-adrenergic receptor is mutant in cortical myoclonus and epilepsy, Ann Neurol 75 :77–87, 2014. Crossref, MedlineGoogle Scholar
    • 45. Shibasaki K, Ikenaka K, Tamalu F et al., A novel subtype of astrocytes expressing TRPV4 (transient receptor potential vanilloid 4) regulates neuronal excitability via the release of gliotransmitters, J Biol Chem 289 :14470–14480, 2014. Crossref, MedlineGoogle Scholar
    • 46. Sima X, Xu J, Li J et al., Expression of β-amyloid precursor protein in refractory epilepsy, Mol Med Rep 9 :1242–1248, 2014. Crossref, MedlineGoogle Scholar
    • 47. Tang L, Zhang Y, Chen G et al., Down-regulation of Pin1 in temporal lobe epilepsy patients and mouse model, Neurochem Res 42 :1211–1218, 2017. Crossref, MedlineGoogle Scholar