In silico analysis identified potential interaction between glutathione and spliceosome in Nager Syndrome

Area of Science:

• Genetics and Developmental Biology
• Pharmacology and Toxicology
• Bioinformatics

Background:

• Nager syndrome (NS) is a rare congenital disorder with poorly understood mechanisms, though increased reactive oxygen species (ROS) are implicated.
• Craniofacial anomalies and preaxial limb defects are hallmarks of Nager syndrome.

Purpose of the Study:

• To investigate the potential pharmacological targets and mechanisms of glutathione (GSH) in Nager syndrome.
• To explore GSH's role in craniofacial development within the context of NS.

Main Methods:

• Network pharmacology and bioinformatics analyses were used to identify intersecting targets between GSH and NS.
• Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed.
• Molecular docking simulations (AutoDock Vina) were conducted to assess interactions between GSH and specific proteins.

Main Results:

• 139 intersecting targets between GSH and NS were identified.
• GSH was found to potentially influence RNA splicing pathways crucial for craniofacial morphogenesis.
• Molecular docking revealed potential interactions between GSH and spliceosomopathy-associated proteins: EFTUD2, SF3B2, and EIF4A3.

Conclusions:

• Glutathione (GSH) may ameliorate craniofacial abnormalities in Nager syndrome (NS) through modulation of RNA splicing pathways.
• The study provides potential molecular mechanisms for GSH's therapeutic effects in NS and related craniofacial spliceosomopathies.
• These findings suggest new directions for functional validation and therapeutic development for Nager syndrome.