Multiomic analysis implicates nuclear hormone receptor signalling in clustering epilepsy.
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
27 Jan 2024
27 Jan 2024
Historique:
received:
03
07
2023
accepted:
16
01
2024
revised:
07
01
2024
medline:
28
1
2024
pubmed:
28
1
2024
entrez:
27
1
2024
Statut:
epublish
Résumé
Clustering Epilepsy (CE) is an epileptic disorder with neurological comorbidities caused by heterozygous variants of the X chromosome gene Protocadherin 19 (PCDH19). Recent studies have implicated dysregulation of the Nuclear Hormone Receptor (NHR) pathway in CE pathogenesis. To obtain a comprehensive overview of the impact and mechanisms of loss of PCDH19 function in CE pathogenesis, we have performed epigenomic, transcriptomic and proteomic analysis of CE relevant models. Our studies identified differential regulation and expression of Androgen Receptor (AR) and its targets in CE patient skin fibroblasts. Furthermore, our cell culture assays revealed the repression of PCDH19 expression mediated through ERα and the co-regulator FOXA1. We also identified a protein-protein interaction between PCDH19 and AR, expanding upon the intrinsic link between PCDH19 and the NHR pathway. Together, these results point to a novel mechanism of NHR signaling in the pathogenesis of CE that can be explored for potential therapeutic options.
Identifiants
pubmed: 38280856
doi: 10.1038/s41398-024-02783-5
pii: 10.1038/s41398-024-02783-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
65Subventions
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : 44131150
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : 44131150
Informations de copyright
© 2024. The Author(s).
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