Insights into Human Epileptogenesis with Proteomic Profiling

Abstract

Epilepsy affects millions globally, and drug-resistant epilepsy remains a challenge. Molecular mechanisms underlying epilepsy remain elusive. Protein profiling through proteomics offers insight into biomarkers and therapeutic targets. Human brain tissue from epilepsy surgeries was analyzed using data-independent acquisition (DIA) proteomics. Samples were categorized into Core (epileptogenic focus), Border (marginal excision tissue), and Nonepileptic control groups. Differential expression proteins (DEPs) were identified and shared proteins were analyzed. 163 DEPs were identified which may has potential roles in the initiation of epileptic electrical firing, 412 DEPs which indicating the difference between epilepsy and Nonepilepsy patients and 10 DEPs consistently altered in Core which indicating potential roles in epileptogenesis. Notably, P35754/GLRX, O75335/PPFIA4, and Q96KP4/CNDP2 were consistently expressed differently in all group pairs. From validation experiments, the expression of Kv3.2 significant reduced in the Core group compare to border group by immunohistochemistry and knockdown of Kv3.2 increased seizure susceptibility and altered neuronal excitability through our cellular and animal experimentation.