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The Sodium Channel B4-Subunits are Dysregulated in Temporal Lobe Epilepsy Drug-Resistant Patients

Temporal lobe epilepsy (TLE) is the most common type of partial epilepsy referred for surgery due to antiepileptic drug (AED) resistance. A common molecular target for many of these drugs is the voltage-gated sodium channel (VGSC). The VGSC consists of four domains of pore-forming α-subunits and two...

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Autores principales: Sheilabi, Mariam A., Takeshita, Louise Y., Sims, Edward J., Falciani, Francesco, Princivalle, Alessandra P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216270/
https://www.ncbi.nlm.nih.gov/pubmed/32331418
http://dx.doi.org/10.3390/ijms21082955
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author Sheilabi, Mariam A.
Takeshita, Louise Y.
Sims, Edward J.
Falciani, Francesco
Princivalle, Alessandra P.
author_facet Sheilabi, Mariam A.
Takeshita, Louise Y.
Sims, Edward J.
Falciani, Francesco
Princivalle, Alessandra P.
author_sort Sheilabi, Mariam A.
collection PubMed
description Temporal lobe epilepsy (TLE) is the most common type of partial epilepsy referred for surgery due to antiepileptic drug (AED) resistance. A common molecular target for many of these drugs is the voltage-gated sodium channel (VGSC). The VGSC consists of four domains of pore-forming α-subunits and two auxiliary β-subunits, several of which have been well studied in epileptic conditions. However, despite the β4-subunits’ role having been reported in some neurological conditions, there is little research investigating its potential significance in epilepsy. Therefore, the purpose of this work was to assess the role of SCN4β in epilepsy by using a combination of molecular and bioinformatics approaches. We first demonstrated that there was a reduction in the relative expression of SCN4B in the drug-resistant TLE patients compared to non-epileptic control specimens, both at the mRNA and protein levels. By analyzing a co-expression network in the neighborhood of SCN4B we then discovered a linkage between the expression of this gene and K(+) channels activated by Ca(2+), or K(+) two-pore domain channels. Our approach also inferred several potential effector functions linked to variation in the expression of SCN4B. These observations support the hypothesis that SCN4B is a key factor in AED-resistant TLE, which could help direct both the drug selection of TLE treatments and the development of future AEDs.
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spelling pubmed-72162702020-05-22 The Sodium Channel B4-Subunits are Dysregulated in Temporal Lobe Epilepsy Drug-Resistant Patients Sheilabi, Mariam A. Takeshita, Louise Y. Sims, Edward J. Falciani, Francesco Princivalle, Alessandra P. Int J Mol Sci Article Temporal lobe epilepsy (TLE) is the most common type of partial epilepsy referred for surgery due to antiepileptic drug (AED) resistance. A common molecular target for many of these drugs is the voltage-gated sodium channel (VGSC). The VGSC consists of four domains of pore-forming α-subunits and two auxiliary β-subunits, several of which have been well studied in epileptic conditions. However, despite the β4-subunits’ role having been reported in some neurological conditions, there is little research investigating its potential significance in epilepsy. Therefore, the purpose of this work was to assess the role of SCN4β in epilepsy by using a combination of molecular and bioinformatics approaches. We first demonstrated that there was a reduction in the relative expression of SCN4B in the drug-resistant TLE patients compared to non-epileptic control specimens, both at the mRNA and protein levels. By analyzing a co-expression network in the neighborhood of SCN4B we then discovered a linkage between the expression of this gene and K(+) channels activated by Ca(2+), or K(+) two-pore domain channels. Our approach also inferred several potential effector functions linked to variation in the expression of SCN4B. These observations support the hypothesis that SCN4B is a key factor in AED-resistant TLE, which could help direct both the drug selection of TLE treatments and the development of future AEDs. MDPI 2020-04-22 /pmc/articles/PMC7216270/ /pubmed/32331418 http://dx.doi.org/10.3390/ijms21082955 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sheilabi, Mariam A.
Takeshita, Louise Y.
Sims, Edward J.
Falciani, Francesco
Princivalle, Alessandra P.
The Sodium Channel B4-Subunits are Dysregulated in Temporal Lobe Epilepsy Drug-Resistant Patients
title The Sodium Channel B4-Subunits are Dysregulated in Temporal Lobe Epilepsy Drug-Resistant Patients
title_full The Sodium Channel B4-Subunits are Dysregulated in Temporal Lobe Epilepsy Drug-Resistant Patients
title_fullStr The Sodium Channel B4-Subunits are Dysregulated in Temporal Lobe Epilepsy Drug-Resistant Patients
title_full_unstemmed The Sodium Channel B4-Subunits are Dysregulated in Temporal Lobe Epilepsy Drug-Resistant Patients
title_short The Sodium Channel B4-Subunits are Dysregulated in Temporal Lobe Epilepsy Drug-Resistant Patients
title_sort sodium channel b4-subunits are dysregulated in temporal lobe epilepsy drug-resistant patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216270/
https://www.ncbi.nlm.nih.gov/pubmed/32331418
http://dx.doi.org/10.3390/ijms21082955
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