Elsevier

EBioMedicine

Volume 45, July 2019, Pages 646-654
EBioMedicine

Review
Targeting microRNA-134 for seizure control and disease modification in epilepsy

https://doi.org/10.1016/j.ebiom.2019.07.008Get rights and content
Under a Creative Commons license
open access

Abstract

MicroRNA-134 is a brain-enriched small noncoding RNA that has been implicated in diverse neuronal functions, including regulating network excitability. Increased expression of microRNA-134 has been reported in several experimental epilepsy models and in resected brain tissue from temporal lobe epilepsy patients. Rodent studies have demonstrated that reducing microRNA-134 expression in the brain using antisense oligonucleotides can increase seizure thresholds and attenuate status epilepticus. Critically, inhibition of microRNA-134 after status epilepticus can potently reduce the occurrence of spontaneous recurrent seizures. Altered plasma levels of microRNA-134 have been reported in epilepsy patients, suggesting microRNA-134 may have diagnostic value as a biomarker. This review summarises findings on the cellular functions of microRNA-134, as well as the preclinical evidence supporting anti-seizure and disease-modifying effects of targeting microRNA-134 in epilepsy. Finally, we draw attention to unanswered questions and some of the challenges and opportunities involved in preclinical development of a microRNA-based oligonucleotide treatment for epilepsy.

Keywords

Epileptogenesis
Noncoding RNA
Hippocampal sclerosis
Biomarker
RNA therapy

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Authors contributed equally to the manuscript.