TY - JOUR

T1 - Forward Genetics-Based Approaches to Understanding the Systems Biology and Molecular Mechanisms of Epilepsy

AU - Shevlyakov, Anton D.

AU - Kolesnikova, Tatiana O.

AU - De abreu, Murilo S.

AU - Petersen, Elena V.

AU - Yenkoyan, Konstantin B.

AU - Demin, Konstantin A.

AU - Kalueff, Allan V.

N1 - The study was performed in collaboration with the YSMU COBRAIN Scientific-Educational Center for Fundamental Brain Research, supported by the Republic of Armenia State Committee of Science (20TTCG-3A012 and N10-14/I-1) and the European Union-funded H2020 COBRAIN project (857600). The research was supported by Sirius University of Science and Technology Project ID NRB-RND-2116. K.A.D. was supported by St. Petersburg State University state budgetary funds (Project ID 93020614). The study partially used the facilities and equipment of the Resource Fund of Applied Genetics MIPT (support grant 075-15-2021-684).

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

UR - https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=tsmetrics&SrcApp=tsm_test&DestApp=WOS_CPL&DestLinkType=FullRecord&KeyUT=000959151300001

UR - http://www.scopus.com/inward/record.url?partnerID=8YFLogxK&scp=85151110646

U2 - 10.3390/ijms24065280

DO - 10.3390/ijms24065280

M3 - Review article

VL - 24

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 6

M1 - 5280

ER -