Emerging Molecular Targets for Anti-Epileptogenic and Epilepsy Modifying Drugs

The pharmacological treatment of epilepsy is purely symptomatic. Despite many decades of intensive research, causal treatment of this common neurologic disorder is still unavailable. Nevertheless, it is expected that advances in modern neuroscience and molecular biology tools, as well as improved animal models may accelerate designing antiepileptogenic and epilepsy-modifying drugs. Epileptogenesis triggers a vast array of genomic, epigenomic and transcriptomic changes, which ultimately lead to morphological and functional transformation of specific neuronal circuits resulting in the occurrence of spontaneous convulsive or nonconvulsive seizures. Recent decades unraveled molecular processes and biochemical signaling pathways involved in the proepileptic transformation of brain circuits including oxidative stress, apoptosis, neuroinflammatory and neurotrophic factors. The omics data derived from both human and animal epileptic tissues, as well as electrophysiological, imaging and neurochemical analysis identified a plethora of possible molecular targets for drugs, which could interfere with various stages of epileptogenetic cascade, including inflammatory processes and neuroplastic changes. In this narrative review, we briefly present contemporary views on the neurobiological background of epileptogenesis and discuss the advantages and disadvantages of some more promising molecular targets for antiepileptogenic pharmacotherapy.

Automated summary

The pharmacological treatment of epilepsy is only aimed at relieving symptoms. Despite years of research, a causal treatment for this common neurological disorder is still unavailable. Advances in neuroscience and molecular biology tools, as well as improved animal models, may accelerate the development of antiepileptogenic and epilepsy-modifying drugs. Epileptogenesis triggers various changes in the genome, epigenome, and transcriptome, leading to the transformation of neuronal circuits and the occurrence of seizures.