Identification of gene regulatory networks affected across drug-resistant epilepsies
Abstract Epilepsy is a chronic and heterogenous disease characterized by recurrent unprovoked seizures, that are commonly resistant to antiseizure medications. This study applies a transcriptome network-based approach across epilepsies aiming to improve understanding of molecular disease pathobiolog...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-46592-2 |
| _version_ | 1797259248905748480 |
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| author | Liesbeth François Alessia Romagnolo Mark J. Luinenburg Jasper J. Anink Patrice Godard Marek Rajman Jonathan van Eyll Angelika Mühlebner Andrew Skelton James D. Mills Stefanie Dedeurwaerdere Eleonora Aronica |
| author_facet | Liesbeth François Alessia Romagnolo Mark J. Luinenburg Jasper J. Anink Patrice Godard Marek Rajman Jonathan van Eyll Angelika Mühlebner Andrew Skelton James D. Mills Stefanie Dedeurwaerdere Eleonora Aronica |
| author_sort | Liesbeth François |
| collection | DOAJ |
| description | Abstract Epilepsy is a chronic and heterogenous disease characterized by recurrent unprovoked seizures, that are commonly resistant to antiseizure medications. This study applies a transcriptome network-based approach across epilepsies aiming to improve understanding of molecular disease pathobiology, recognize affected biological mechanisms and apply causal reasoning to identify therapeutic hypotheses. This study included the most common drug-resistant epilepsies (DREs), such as temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), and mTOR pathway-related malformations of cortical development (mTORopathies). This systematic comparison characterized the global molecular signature of epilepsies, elucidating the key underlying mechanisms of disease pathology including neurotransmission and synaptic plasticity, brain extracellular matrix and energy metabolism. In addition, specific dysregulations in neuroinflammation and oligodendrocyte function were observed in TLE-HS and mTORopathies, respectively. The aforementioned mechanisms are proposed as molecular hallmarks of DRE with the identified upstream regulators offering opportunities for drug-target discovery and development. |
| first_indexed | 2024-04-24T23:06:25Z |
| format | Article |
| id | doaj.art-d55463fe03e3422294e40f44397850cb |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T23:06:25Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-d55463fe03e3422294e40f44397850cb2024-03-17T12:30:11ZengNature PortfolioNature Communications2041-17232024-03-0115111710.1038/s41467-024-46592-2Identification of gene regulatory networks affected across drug-resistant epilepsiesLiesbeth François0Alessia Romagnolo1Mark J. Luinenburg2Jasper J. Anink3Patrice Godard4Marek Rajman5Jonathan van Eyll6Angelika Mühlebner7Andrew Skelton8James D. Mills9Stefanie Dedeurwaerdere10Eleonora Aronica11UCB Pharma, Early SolutionsDepartment of (Neuro)Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam NeuroscienceDepartment of (Neuro)Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam NeuroscienceDepartment of (Neuro)Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam NeuroscienceUCB Pharma, Early SolutionsUCB Pharma, Early SolutionsUCB Pharma, Early SolutionsDepartment of (Neuro)Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam NeuroscienceUCB Pharma, Early SolutionsDepartment of (Neuro)Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam NeuroscienceUCB Pharma, Early SolutionsDepartment of (Neuro)Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam NeuroscienceAbstract Epilepsy is a chronic and heterogenous disease characterized by recurrent unprovoked seizures, that are commonly resistant to antiseizure medications. This study applies a transcriptome network-based approach across epilepsies aiming to improve understanding of molecular disease pathobiology, recognize affected biological mechanisms and apply causal reasoning to identify therapeutic hypotheses. This study included the most common drug-resistant epilepsies (DREs), such as temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), and mTOR pathway-related malformations of cortical development (mTORopathies). This systematic comparison characterized the global molecular signature of epilepsies, elucidating the key underlying mechanisms of disease pathology including neurotransmission and synaptic plasticity, brain extracellular matrix and energy metabolism. In addition, specific dysregulations in neuroinflammation and oligodendrocyte function were observed in TLE-HS and mTORopathies, respectively. The aforementioned mechanisms are proposed as molecular hallmarks of DRE with the identified upstream regulators offering opportunities for drug-target discovery and development.https://doi.org/10.1038/s41467-024-46592-2 |
| spellingShingle | Liesbeth François Alessia Romagnolo Mark J. Luinenburg Jasper J. Anink Patrice Godard Marek Rajman Jonathan van Eyll Angelika Mühlebner Andrew Skelton James D. Mills Stefanie Dedeurwaerdere Eleonora Aronica Identification of gene regulatory networks affected across drug-resistant epilepsies Nature Communications |
| title | Identification of gene regulatory networks affected across drug-resistant epilepsies |
| title_full | Identification of gene regulatory networks affected across drug-resistant epilepsies |
| title_fullStr | Identification of gene regulatory networks affected across drug-resistant epilepsies |
| title_full_unstemmed | Identification of gene regulatory networks affected across drug-resistant epilepsies |
| title_short | Identification of gene regulatory networks affected across drug-resistant epilepsies |
| title_sort | identification of gene regulatory networks affected across drug resistant epilepsies |
| url | https://doi.org/10.1038/s41467-024-46592-2 |
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