MicroRNA Dysregulation in Epilepsy: From Pathogenetic Involvement to Diagnostic Biomarker and Therapeutic Agent Development

Abstract

Epilepsy is the result of a group of transient abnormalities in brain function caused by an abnormal, highly synchronized discharge of brain neurons. MicroRNA (miRNA) is a class of endogenous non-coding single-stranded RNA molecules that participate in a series of important biological processes. Recent studies demonstrated that miRNAs are involved in a variety of central nervous system diseases, including epilepsy. Although the exact mechanism underlying the role of miRNAs in epilepsy pathogenesis is still unclear, these miRNAs may be involved in the inflammatory response in the nervous system, neuronal necrosis and apoptosis, dendritic growth, synaptic remodeling, glial cell proliferation, epileptic circuit formation, impairment of neurotransmitter and receptor function, and other processes. Here, we discuss miRNA metabolism and the roles of miRNA in epilepsy pathogenesis and evaluate miRNA as a potential new biomarker for the diagnosis of epilepsy, which enhances our understanding of disease processes.

Non-Coding RNAs: New Biomarkers and Therapeutic Targets for Temporal Lobe Epilepsy

“…Several functional studies suggest that miRNAs may be involved in the occurrence and development of epilepsy by affecting these pathological processes. Much evidence underlies the involvement of miRNAs in the inflammatory and immune process in TLE, and, about this, their role has been extensively studied [ 29 ]. Alteration in miRNA expression may be involved in epilepsy pathogenesis by regulating the expression of inflammatory factors, such as IL-1, INF-α and TNF-α.…”

Regulation of microRNA Expression in Sleep Disorders in Patients with Epilepsy

“…Landau–Kleffner syndrome and continuous spike wave in slow-wave sleep (CSWS) can be associated with the electrical status epilepticus in sleep (ESES) described as an electroencephalographic pattern showing significant activation of epileptiform discharges in sleep [ 28 ]. In animal models of status epilepticus, miRNA-23a was upregulated in the hippocampus after status epilepticus [ 29 , 30 ].…”

Molecular Chaperones and miRNAs in Epilepsy: Pathogenic Implications and Therapeutic Prospects

“…Over 2000 human miRNAs have been discovered thus far, which regulate the vast majority of protein-encoding genes, and, thus, affect most, if not all, biological events, including cell proliferation, differentiation, and death, playing a significant role during various stages of growth and development [29][30][31][32]. Multiple studies have investigated the variation of miRNA expression patterns in various neurological diseases, including epilepsy, to assess their role in disease pathogenesis and their usefulness as diagnostic biomarkers, as well as to develop efficacious therapeutic strategies [33,34]. Different miRNAs have been implicated in a variety of processes involved in epileptogenesis, such as neuroinflammation, blood brain barrier (BBB) dysfunctions, apoptosis, ion channel dysregulation, axonal guidance, and synaptic plasticity [35][36][37][38][39][40][41][42][43][44], all of which point to them as promising therapeutic targets [45,46] (Figure 1, Table 1).…”

“…Chaperone-induced inhibition Increase in glutamate transporter-1 (GLT-1) and seizure suppression [70,71] MiRNAs and Epilepsy miRNAs may be involved in the development of epilepsy by regulating those pathological processes mediating epileptogenesis, such as neuroinflammation, neuronal cell death, synaptic remodeling, formation of epileptic circuits, deregulation of neurotrophic factors, and glial cell dysfunction [34]. miRNA expression patterns may be useful for diagnosis and prognostication.…”