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

Author:

Shevlyakov Anton D.12,Kolesnikova Tatiana O.2,de Abreu Murilo S.3ORCID,Petersen Elena V.3,Yenkoyan Konstantin B.4ORCID,Demin Konstantin A.56ORCID,Kalueff Allan V.2456789ORCID

Affiliation:

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

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.

Funder

Sirius University of Science and Technology

St. Petersburg State University state budgetary funds

Resource Fund of Applied Genetics MIPT

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Reference74 articles.

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