microRNA- based Novel Therapeutic Approach in Epilepsy

Epilepsy, the fourth most common severe neurological disorder, is characterized by recurrent unprovokedseizures, and mainly caused by malfunction of involved genes in different pathways such as inflammation, neuralfunction, and synaptic structure as a result of either brain injury or positive family history. Since currentAntiepileptic Drugs (AEDs) are almost ineffective in one-third cases of epilepsy, the demand for diseasemodifyingdrugs mainly targeting the key components of mentioned pathways is increasing dramatically.microRNAs (miRNAs), as small non-coding endogenous RNAs with 19-24 nucleotides in length, are posttranscriptionalregulators of nearly 60% of protein-coding genes through binding to 3′ UTR of target mRNAs andleading translational inhibition. Based on the newly established database on miRNAs in Epilepsy (EpimiRBase),dysregulated microRNAs linked to this neurological condition divide into two groups of up-regulated (such asmiR-34, miR-132, miR-134, miR-181-a, miR-199a, and miR-210) and down-regulated miRNAs (such as miR-128, miR-219, miR-23-b, miR-124). Among these microRNAs, miR-124 is a brain-specific microRNA whichsuppresses seizures recurrence through regulating cAMP-response element-binding protein1 (CREB1) activityand contributes to synaptic plasticity and neural excitability. Since seizure attacks have been reduced throughimplementation of miR-124, systemic injection of the miRNAs encapsulated in nanoparticles (or other deliverysystems including cell- penetration peptides or exosome-based approach) containing miR-124 AntagomiR, alarge anti-sense like molecule, would be an appropriate candidate for microRNA-based drugs in prevention andtreatment of human Epilepsy. Recent findings express the novel therapeutic role of miR-124 in human epilepsyas it could reduce the seizures attacks.

کلیدواژه ها:

Epilepsy ، microRNA ، miR-124 ، EpimiRBase