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

Abstract

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy; it is considered a network disorder associated with structural changes. Incomplete knowledge of the pathological changes in TLE complicates a therapeutic approach; indeed, 30 to 50% of patients with TLE are refractory to drug treatment. Non-coding RNAs (ncRNAs), acting as epigenetic factors, participate in the regulation of the pathophysiological processes of epilepsy and are dysregulated during epileptogenesis. Abnormal expression of ncRNA is observed in patients with epilepsy and in animal models of epilepsy. Furthermore, ncRNAs could also be used as biomarkers for the diagnosis and prognosis of treatment response in epilepsy. In summary, ncRNAs can represent important mechanisms and targets for the modulation of brain excitability and can provide information on pathomechanisms, biomarkers and novel therapies for epilepsy. In this review, we summarize the latest research advances concerning mainly molecular mechanisms, regulated by ncRNA, such as synaptic plasticity, inflammation and apoptosis, already associated with the pathogenesis of TLE. Moreover, we discuss the role of ncRNAs, such as microRNAs, long non-coding RNAs and circular RNAs, in the pathophysiology of epilepsy, highlighting their use as potential biomarkers for future therapeutic approaches.

Keywords: biomarker; circular RNA; long non-coding RNA; microRNA; non-coding RNAs; therapeutic target.

Figure 1

Schematic representation of ncRNA mechanisms of action. ncRNAs regulate gene expression both at transcriptional and post-transcriptional levels. miRNA, lncRNA and circRNA act in a variety of ways, promoting or inhibiting the expression of specific targets. Mechanisms of action of ncRNAs are summarized within each box.