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

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 epile...

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Autores principales: Morris, Gareth, Reschke, Cristina R., Henshall, David C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642437/
https://www.ncbi.nlm.nih.gov/pubmed/31300345
http://dx.doi.org/10.1016/j.ebiom.2019.07.008
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author Morris, Gareth
Reschke, Cristina R.
Henshall, David C.
author_facet Morris, Gareth
Reschke, Cristina R.
Henshall, David C.
author_sort Morris, Gareth
collection PubMed
description 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.
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spelling pubmed-66424372019-07-23 Targeting microRNA-134 for seizure control and disease modification in epilepsy Morris, Gareth Reschke, Cristina R. Henshall, David C. EBioMedicine Review 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. Elsevier 2019-07-09 /pmc/articles/PMC6642437/ /pubmed/31300345 http://dx.doi.org/10.1016/j.ebiom.2019.07.008 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Review
Morris, Gareth
Reschke, Cristina R.
Henshall, David C.
Targeting microRNA-134 for seizure control and disease modification in epilepsy
title Targeting microRNA-134 for seizure control and disease modification in epilepsy
title_full Targeting microRNA-134 for seizure control and disease modification in epilepsy
title_fullStr Targeting microRNA-134 for seizure control and disease modification in epilepsy
title_full_unstemmed Targeting microRNA-134 for seizure control and disease modification in epilepsy
title_short Targeting microRNA-134 for seizure control and disease modification in epilepsy
title_sort targeting microrna-134 for seizure control and disease modification in epilepsy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642437/
https://www.ncbi.nlm.nih.gov/pubmed/31300345
http://dx.doi.org/10.1016/j.ebiom.2019.07.008
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