Targeting microRNA-134 for seizure control and.....pdf (1.52 MB)

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

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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.

Funding

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

History

Comments

The original article is available at https://www.sciencedirect.com/

Published Citation

Morris G, Reschke CR, Henshall DC. Targeting microRNA-134 for seizure control and disease modification in epilepsy. EBioMedicine. 2019 45:646-654.

Publication Date

9 July 2019

PubMed ID

31300345

Department/Unit

  • FutureNeuro Centre
  • Physiology and Medical Physics

Research Area

  • Neurological and Psychiatric Disorders

Publisher

Elsevier

Version

  • Published Version (Version of Record)