Alternative splicing in voltage-gated sodium channels: mechanisms, regulatory networks and therapeutic implications - PubMed
4 hours ago
- #channelopathies
- #alternative-splicing
- #voltage-gated-sodium-channels
- Voltage-gated sodium channels (VGSCs) are crucial for electrical signaling in excitable cells and their dysfunction leads to channelopathies.
- Alternative splicing significantly expands the proteomic and functional diversity of VGSCs beyond the nine distinct α-subunit genes.
- Dysregulation of alternative splicing in VGSCs is increasingly associated with disease pathogenesis.
- The review catalogs splicing variants across all nine VGSC α-subunits, detailing their roles in development, tissue-specific expression, and channel biophysics.
- Key RNA-binding proteins (RBPs) like Rbfox and Nova2 regulate splicing events within cell-type-specific networks.
- Splicing dysregulation contributes to channelopathies, and antisense oligonucleotides (ASOs) offer a promising therapeutic approach to correct these defects.
- The review emphasizes the need for precision medicine targeting splicing defects in VGSC-associated disorders.