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

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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. .

In: International Journal of Molecular Sciences, Vol. 24, No. 6, 5280, 09.03.2023.

Research output: Contribution to journal › Review article › peer-review

BibTeX

@article{f7ad32c742b84432a4f0ffaeb3d6116c,

title = "Forward Genetics-Based Approaches to Understanding the Systems Biology and Molecular Mechanisms of Epilepsy",

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 NETWORKING, in silico modeling, Epilepsy/drug therapy, Seizures/drug therapy, Humans, Genome, Systems Biology, Anticonvulsants/therapeutic use",

author = "Shevlyakov, {Anton D.} and Kolesnikova, {Tatiana O.} and {de Abreu}, {Murilo S} and Petersen, {Elena V.} and Yenkoyan, {Konstantin B} and Demin, {Konstantin A.} and Kalueff, {Allan V.}",

note = "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",

year = "2023",

month = mar,

day = "9",

doi = "10.3390/ijms24065280",

language = "English",

volume = "24",

journal = "International Journal of Molecular Sciences",

issn = "1422-0067",

publisher = "MDPI AG",

number = "6",

}

RIS

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 - 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

PY - 2023/3/9

Y1 - 2023/3/9

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.

KW - epilepsy

KW - genes

KW - Genetic bases

KW - MOLECULAR NETWORKING

KW - in silico modeling

KW - Epilepsy/drug therapy

KW - Seizures/drug therapy

KW - Humans

KW - Genome

KW - Systems Biology

KW - Anticonvulsants/therapeutic use

UR - https://www.mendeley.com/catalogue/8d2a8f6f-003a-3fcb-b6dd-3dc644793096/

U2 - 10.3390/ijms24065280

DO - 10.3390/ijms24065280

M3 - Review article

C2 - 36982355

VL - 24

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 6

M1 - 5280

ER -

ID: 106447427