Epilepsy in Neurodegenerative Diseases: Related Drugs and Molecular Pathways

Abstract

Epilepsy is a chronic disease of the central nervous system characterized by an electrical imbalance in neurons. It is the second most prevalent neurological disease, with 50 million people affected around the world, and 30% of all epilepsies do not respond to available treatments. Currently, the main hypothesis about the molecular processes that trigger epileptic seizures and promote the neurotoxic effects that lead to cell death focuses on the exacerbation of the glutamate pathway and the massive influx of Ca2+ into neurons by different factors. However, other mechanisms have been proposed, and most of them have also been described in other neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, or multiple sclerosis. Interestingly, and mainly because of these common molecular links and the lack of effective treatments for these diseases, some antiseizure drugs have been investigated to evaluate their therapeutic potential in these pathologies. Therefore, in this review, we thoroughly investigate the common molecular pathways between epilepsy and the major neurodegenerative diseases, examine the incidence of epilepsy in these populations, and explore the use of current and innovative antiseizure drugs in the treatment of refractory epilepsy and other neurodegenerative diseases.

Central nervous system effects of 5-HT7 receptors: a potential target for neurodegenerative diseases

“…Epilepsy-induced neuronal damage shares pathophysiological neurodegenerative features with dementias and other CNS diseases, such as increased inflammation and excitotoxicity (Nikiforuk 2015 ). Epilepsy is prevalent in sufferers of CNS diseases, including AD, PD, or HD, and, when present, indicates a higher burden of neurodegeneration (Cano et al 2021 ).…”

Obesity and the Brain

“…Although bacterial metabolites such as polysaccharide A and short-chain fatty acids (SCFAs) can induce regulatory T (Treg) cells, the specific microbial factors responsible for pathogenic T cells activation remain unknown [ 57 ]. The numerical/functional deficits in the Treg cells subpopulation have also been suggested to play an important role in MS immunopathology [ 58 , 59 ], as well as B cells, which is supported by the positive effects of B cell-depleting therapies [ 60 ]. Relapses in MS subjects are affected by stressful events and infections, most frequently those of the upper respiratory tract [ 61 ].…”

“…Relapses in MS subjects are affected by stressful events and infections, most frequently those of the upper respiratory tract [ 61 ]. Although a specific autoantigen in MS has not been identified yet, autoreactive T cells are assumed to target proteins of the myelin sheath, causing demyelination and, thereby, white matter damage [ 57 , 59 , 62 ]. Demyelination deprives neurons of protective factors and has been described to decrease axonal transport and synaptic density in demyelinated hippocampi [ 63 ].…”

Biodegradable nanoparticles for the treatment of epilepsy: From current advances to future challenges

“…5,9 Due to this fact, the third-generation ASM (lacosamide, rufinamide, ezogabine, eslicarbazepine, and perampanel) emerged with a more favorable pharmacokinetic profile and increased control of neuronal excitability to prevent epileptic seizure. 10 In general, their mechanism of action is focused on the decrease or modulation of neuronal excitability, 11 which in turn stops the expansion of electrical discharges at the brain level. 12 The mechanism of action of ASM is related to different therapeutic targets and therefore they can be classified in different groups 13 (Table 1).…”

“…In general, their mechanism of action is focused on the decrease or modulation of neuronal excitability, 11 which in turn stops the expansion of electrical discharges at the brain level. 12 The mechanism of action of ASM is related to different therapeutic targets and therefore they can be classified in different groups 13 (Table 1 ).…”