MiRNA Dysregulation in Epilepsy: Bridging Molecular Mechanisms and Therapeutic Innovation

MicroRNAs (miRNAs), small non-coding RNA molecules, have been considered as pivotal regulators of gene expression, influencing many biological functions, including nerve cell development, synaptic plasticity, and inflammatory responses. Their biogenesis involves a multi-step process, beginning with transcription by RNA polymerase II, followed by processing through Drosha and Dicer enzymes, culminating in the formation of mature miRNAs that integrate into the RNA-induced silencing complex [1] to control target messenger RNA (mRNA) stability and translation. In the context of epilepsy, a neurological disorder characterized by recurrent seizures, miRNAs have a role in the modulation of neuronal excitability and network synchronization. Dysregulation of specific miRNAs can disrupt the delicate balance between excitatory and inhibitory neurotransmission, contributing to the pathogenesis of epilepsy. Moreover, miRNAs influence neuroplasticity by regulating genes involved in synaptic remodeling and neuronal connectivity, processes that are often aberrant in epileptic brains. Inflammatory pathways are also modulated by miRNAs, with certain miRNAs acting as key regulators of cytokine expression and immune cell activation, thereby influencing neuroinflammation associated with epileptogenesis. Clinically, altered miRNA expression profiles have been shown in the blood and cerebrospinal fluid of epilepsy patients, suggesting their potential as non-invasive biomarkers for diagnosis and prognosis. Furthermore, therapeutic strategies targeting miRNAs are being explored, aiming to restore normal gene expression patterns and mitigate seizure activity. This review delves into the intricate roles of miRNAs in epilepsy, encompassing their biogenesis, involvement in disease pathophysiology, impact on neuroplasticity and inflammation, and their emerging clinical applications.