Targeting microRNA-134 for seizure control and disease modification in epilepsy
journal contributionposted on 16.08.2021, 15:44 by Gareth MorrisGareth Morris, Cristina Ruedell ReschkeCristina Ruedell Reschke, David HenshallDavid Henshall
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.
Health Research Board Ireland (HRA-POR-2013-325)
Science Foundation Ireland (13/IA/1891, 11/TIDA/B1988)
Irish Research Council and the European Union Seventh Framework Programme (FP7/2007- 2013) grant agreement no. 602130 (EpimiRNA)
Scoience Foundation Ireland (SFI) Grant Number 16/ RC/3948
European Regional Development Fund
FutureNeuro industry partners
CommentsThe original article is available at https://www.sciencedirect.com/
Published CitationMorris G, Reschke CR, Henshall DC. Targeting microRNA-134 for seizure control and disease modification in epilepsy. EBioMedicine. 2019 45:646-654.
Publication Date9 July 2019
- FutureNeuro Centre
- Physiology and Medical Physics
- Neurological and Psychiatric Disorders
- Published Version (Version of Record)