Forward Genetics-Based Approaches to Understanding the Systems Biology and Molecular Mechanisms of Epilepsy

Shevlyakov, Anton D.; Kolesnikova, Tatiana O.; de Abreu, Murilo S.; Petersen, Elena V.; Yenkoyan, Konstantin B.; Demin, Konstantin A.; Kalueff, Allan V.

doi:10.3390/ijms24065280

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Forward Genetics-Based Approaches to Understanding the Systems Biology and Molecular Mechanisms of Epilepsy

by

Anton D. Shevlyakov

^1,2

,

Tatiana O. Kolesnikova

²,

Murilo S. de Abreu

³

,

Elena V. Petersen

³,

Konstantin B. Yenkoyan

⁴

,

Konstantin A. Demin

^5,6,*

and

Allan V. Kalueff

^{2,4,5,6,7,8,9,*}

¹

Graduate Program in Bioinformatics and Genomics, Sirius University of Science and Technology, 354340 Sochi, Russia

²

Neuroscience Program, Sirius University of Science and Technology, 354340 Sochi, Russia

³

Moscow Institute of Physics and Technology, 11730 Moscow, Russia

⁴

Neuroscience Laboratory of COBRAIN Center for Fundamental Brain Research, and Biochemistry Department, Yerevan State Medical University named after M. Heratsi, Yerevan 0025, Armenia

⁵

Institute of Translational Biomedicine, St. Petersburg State University, 199034 St. Petersburg, Russia

⁶

Institute of Experimental Medicine, Almazov National Medical Research Centre, Ministry of Healthcare of Russian Federation, 194021 St. Petersburg, Russia

⁷

Laboratory of Preclinical Bioscreening, Granov Russian Research Center of Radiology and Surgical Technologies, Ministry of Healthcare of Russian Federation, 197758 Pesochny, Russia

⁸

Neuroscience Group, Ural Federal University, 620002 Ekaterinburg, Russia

⁹

Laboratory of Biopsychiatry, Scientific Research Institute of Physiology and Basic Medicine, 630117 Novosibirsk, Russia

^*

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2023, 24(6), 5280; https://doi.org/10.3390/ijms24065280

Submission received: 31 December 2022 / Revised: 28 February 2023 / Accepted: 3 March 2023 / Published: 9 March 2023

(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Epilepsy 2.0)

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Abstract

Epilepsy is a highly prevalent, severely debilitating neurological disorder characterized by seizures and neuronal hyperactivity due to an imbalanced neurotransmission. As genetic factors play a key role in epilepsy and its treatment, various genetic and genomic technologies continue to dissect the genetic causes of this disorder. However, the exact pathogenesis of epilepsy is not fully understood, necessitating further translational studies of this condition. Here, we applied a computational in silico approach to generate a comprehensive network of molecular pathways involved in epilepsy, based on known human candidate epilepsy genes and their established molecular interactors. Clustering the resulting network identified potential key interactors that may contribute to the development of epilepsy, and revealed functional molecular pathways associated with this disorder, including those related to neuronal hyperactivity, cytoskeletal and mitochondrial function, and metabolism. While traditional antiepileptic drugs often target single mechanisms associated with epilepsy, recent studies suggest targeting downstream pathways as an alternative efficient strategy. However, many potential downstream pathways have not yet been considered as promising targets for antiepileptic treatment. Our study calls for further research into the complexity of molecular mechanisms underlying epilepsy, aiming to develop more effective treatments targeting novel putative downstream pathways of this disorder.

Keywords: epilepsy; genes; genetic bases; molecular network; in silico modeling

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MDPI and ACS Style

Shevlyakov, A.D.; Kolesnikova, T.O.; de Abreu, M.S.; Petersen, E.V.; Yenkoyan, K.B.; Demin, K.A.; Kalueff, A.V. Forward Genetics-Based Approaches to Understanding the Systems Biology and Molecular Mechanisms of Epilepsy. Int. J. Mol. Sci. 2023, 24, 5280. https://doi.org/10.3390/ijms24065280

AMA Style

Shevlyakov AD, Kolesnikova TO, de Abreu MS, Petersen EV, Yenkoyan KB, Demin KA, Kalueff AV. Forward Genetics-Based Approaches to Understanding the Systems Biology and Molecular Mechanisms of Epilepsy. International Journal of Molecular Sciences. 2023; 24(6):5280. https://doi.org/10.3390/ijms24065280

Chicago/Turabian Style

Shevlyakov, Anton D., Tatiana O. Kolesnikova, Murilo S. de Abreu, Elena V. Petersen, Konstantin B. Yenkoyan, Konstantin A. Demin, and Allan V. Kalueff. 2023. "Forward Genetics-Based Approaches to Understanding the Systems Biology and Molecular Mechanisms of Epilepsy" International Journal of Molecular Sciences 24, no. 6: 5280. https://doi.org/10.3390/ijms24065280

APA Style

Shevlyakov, A. D., Kolesnikova, T. O., de Abreu, M. S., Petersen, E. V., Yenkoyan, K. B., Demin, K. A., & Kalueff, A. V. (2023). Forward Genetics-Based Approaches to Understanding the Systems Biology and Molecular Mechanisms of Epilepsy. International Journal of Molecular Sciences, 24(6), 5280. https://doi.org/10.3390/ijms24065280

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Forward Genetics-Based Approaches to Understanding the Systems Biology and Molecular Mechanisms of Epilepsy

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