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Original Article
Lei Gao
shandong first medical university
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7505-3914
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Stiripentol is an anti-epileptic drug used for treating Dravet syndrome and epilepsy. To explore common molecular mechanism between antiepileptic effect of stiripentol and genetic etiology of Dravet syndrome and epilepsy, we retrieved target genes of stiripentol through DrugBank database, as well as risk genes of Dravet syndrome and epilepsy from related Database and literature research. Then we performed genetic overlap analysis, Expression Weighted Cell type Enrichment (EWCE) analysis based on single-cell RNA-sequencing (scRNA-seq) data of brain, as well as pathway enrichment analysis. A total of 23, 19 and 118 genes were retrieved for stiripentol targets, risk genes of Dravet syndrome and epilepsy respectively. For stiripentol targets and risk genes of Dravet syndrome, three genes (GABRA1, GABRB3 and GABRG2) were overlapped with P-value of 1.265×10−6; hippocampal CA1 pyramidal cells and interneurons were common brain cell types that were significantly enriched by EWCE; and 10 common pathways were identified. For stiripentol targets and risk genes of epilepsy, five genes (GABRA1, GABRA2, GABRB2, GABRB3, and GABRG2) were overlapped with P-value of 1.963 × 10−7; hippocampal CA1 pyramidal cells and interneurons were also common brain cell types that were significantly enriched and 22 common pathways were identified. Our results revealed that stiripentol might exert its anti-epileptic effect by regulating GABAA receptors on hippocampal CA1 pyramidal cells and interneurons.
Keywords
Stiripentol, Epilepsy, Dravet syndrome, Common molecular mechanism, GABAA receptors
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This is a list of supplementary files associated with this preprint. Click to download.
- supplementaryTable.doc
Supplementary Table 1. Dravet syndrome risk genes Supplementary Table 2. Epilepsy risk genes Supplementary Table 3. Enrichment of brain cell types based on mouse brain dataset Supplementary Table 4. Enrichment of brain cell types based on human brain dataset Supplementary Table 5. The pathway enrichment of stiripentol targets Supplementary Table 6. The pathway enrichment of Dravet risk genes Supplementary Table 7. The pathway enrichment of epilepsy risk genes Supplementary Table 8. Common pathways between stiripentol targets and risk genes of Dravet syndrome and epilepsy
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This preprint is under consideration at Molecular Neurobiology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Original Article
Lei Gao
shandong first medical university
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7505-3914
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 02 Feb, 2021
No community comments so far
First submitted
On 21 Jan, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Neurobiology of Disease
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Stiripentol is an anti-epileptic drug used for treating Dravet syndrome and epilepsy. To explore common molecular mechanism between antiepileptic effect of stiripentol and genetic etiology of Dravet syndrome and epilepsy, we retrieved target genes of stiripentol through DrugBank database, as well as risk genes of Dravet syndrome and epilepsy from related Database and literature research. Then we performed genetic overlap analysis, Expression Weighted Cell type Enrichment (EWCE) analysis based on single-cell RNA-sequencing (scRNA-seq) data of brain, as well as pathway enrichment analysis. A total of 23, 19 and 118 genes were retrieved for stiripentol targets, risk genes of Dravet syndrome and epilepsy respectively. For stiripentol targets and risk genes of Dravet syndrome, three genes (GABRA1, GABRB3 and GABRG2) were overlapped with P-value of 1.265×10−6; hippocampal CA1 pyramidal cells and interneurons were common brain cell types that were significantly enriched by EWCE; and 10 common pathways were identified. For stiripentol targets and risk genes of epilepsy, five genes (GABRA1, GABRA2, GABRB2, GABRB3, and GABRG2) were overlapped with P-value of 1.963 × 10−7; hippocampal CA1 pyramidal cells and interneurons were also common brain cell types that were significantly enriched and 22 common pathways were identified. Our results revealed that stiripentol might exert its anti-epileptic effect by regulating GABAA receptors on hippocampal CA1 pyramidal cells and interneurons.
Figure 1
Figure 2
This is a list of supplementary files associated with this preprint. Click to download.
- supplementaryTable.doc
Supplementary Table 1. Dravet syndrome risk genes Supplementary Table 2. Epilepsy risk genes Supplementary Table 3. Enrichment of brain cell types based on mouse brain dataset Supplementary Table 4. Enrichment of brain cell types based on human brain dataset Supplementary Table 5. The pathway enrichment of stiripentol targets Supplementary Table 6. The pathway enrichment of Dravet risk genes Supplementary Table 7. The pathway enrichment of epilepsy risk genes Supplementary Table 8. Common pathways between stiripentol targets and risk genes of Dravet syndrome and epilepsy
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