Emerging Molecular Targets for Anti-Epileptogenic and Epilepsy Modifying Drugs

Abstract

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.

Design and synthesis of novel cycloalkanecarboxamide parabanic acid hybrids as anticonvulsants

“…Consequently, The principal inhibitory neuromediator accountable for the hyperpolarization of every single neuron in the frontal lobe, Gammaaminobutyric acid, may have been involved in the antiepileptic activity of compound 10b. Potentiation of the Gamma-aminobutyric acid action could be ascribed to one of succeeding: (1) binds directly to GABA-A receptors which leads to increment the chloride ions in ow that results in excess negative membrane potential at rest and consequently reducing the of excitation of the membranes located after synapses, (2) increasing Gamma-aminobutyric acid production via glutamic acid decarboxylase enzyme modulation which is responsible for GABA synthesis by decarboxylation of glutamate, (3) inhibition of GABA catabolism through GABA transaminase enzyme suppression or (4) blockage of presynaptic GABA re-uptake [23][24][25].…”

CircRNA‐associated ceRNA regulatory networks as emerging mechanisms governing the development and biophysiopathology of epilepsy

“…The etiology of epilepsy involves a range of factors, including hereditary predisposition as well as symptomatic causes such as brain injuries, tumors, infections, strokes, and developmental abnormalities. 2 Epilepsy is a neurological condition characterized by abnormal nervous transient dysfunction that affects the motor, sensory, consciousness, and autonomic nervous systems and is typically accompanied by abnormal electroencephalograms (EEGs) and pathological abnormalities. 3 Recurrent seizures can exacerbate cerebral dysfunction, induce neuronal damage and necrosis, and potentially lead to fatal outcomes, imposing a substantial burden on the families of individuals affected by this condition.…”

Thalidomide Attenuates Epileptogenesis and Seizures by Decreasing Brain Inflammation in Lithium Pilocarpine Rat Model

“…There is evidence that neuroinflammation plays a key part in epileptogenesis [ 21 , 22 ]. In turn, it affects other processes such as neurogenesis and leads to abnormal reorganization of neuronal networks, mainly in the hippocampus, further promoting neuronal death [ 23 , 24 , 25 ]. Consequently, inhibiting neuroinflammation may be effective for the reduction or even prevention of epileptogenesis.…”