Emerging Molecular Targets for Anti-Epileptogenic and Epilepsy Modifying Drugs.
Katarzyna ŁukasiukWładysław LasońPublished in: International journal of molecular sciences (2023)
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.
Keyphrases
- oxidative stress
- high resolution
- temporal lobe epilepsy
- endothelial cells
- single molecule
- risk assessment
- gene expression
- dna damage
- white matter
- blood brain barrier
- machine learning
- brain injury
- high throughput
- electronic health record
- cerebral ischemia
- subarachnoid hemorrhage
- induced pluripotent stem cells
- resting state
- pi k akt
- high density
- cell cycle arrest