Enhancing KCC2 function reduces interictal activity and prevents seizures in temporal lobe epilepsy - PubMed
3 hours ago
- #KCC2
- #neuropharmacology
- #epilepsy
- Enhancing KCC2 function reduces interictal activity and prevents seizures in temporal lobe epilepsy.
- Two small molecules, prochlorperazine (PCPZ) and CLP-257, identified as potential KCC2 enhancers, were investigated.
- Both compounds enhance KCC2 function and clustering in cortical neurons while reducing its membrane diffusion.
- CLP-257 selectively increased extrasynaptic GABAA receptor-mediated currents.
- PCPZ and CLP-257 (or its prodrug CLP-290) effectively suppressed spontaneous epileptiform activity in human and mouse models.
- Findings support the therapeutic potential of KCC2 enhancers for treating drug-resistant mesial temporal lobe epilepsy (mTLE).