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Cited by 168

MicroRNAs as regulators of brain function and targets for treatment of epilepsy

Brennan, Gary P., Henshall, David C.·2020·Nature Reviews Neurology
DOI 10.1038/s41582-020-0369-8
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Abstract

Seizures result from hypersynchronous, abnormal firing of neuronal populations and are the primary clinical symptom of the epilepsies. Brain tissue from animal models and patients with acquired forms of epilepsy commonly features selective neuronal loss, gliosis, inflammatory markers and microscopic and macroscopic reorganization of networks. The gene expression landscape is a critical driver of these changes, and gene expression is fine tuned by small, non-coding RNAs called microRNAs (miRNAs). miRNAs inhibit the function of protein-coding transcripts, resulting in changes in multiple aspects of cell structure and function, including axonal and dendritic structure and the repertoire of neurotransmitter receptors, ion channels and transporters that establish neurophysiological functions. Dysregulation of the miRNA system has emerged as a mechanism that underlies epileptogenesis. Given that miRNAs can act on multiple mRNA targets, their manipulation offers a novel, multi-targeting approach to correct disturbed gene expression patterns. Targeting of some miRNAs has also been used to selectively upregulate individual transcripts, offering the possibility of precision therapy approaches for disorders of haploinsufficiency. In this Review, we discuss how miRNAs determine and control neuronal and glial functions, how this process is altered in states associated with hyperexcitability, and the prospects for miRNA targeting for the treatment of epilepsy.

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Crossref · 10.1038/s41582-020-0369-8

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16 of 16 references verified0 citation errors · 0 not checkable

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  • miRs are well-established regulators of key brain processes including neurodevelopment, synaptic plasticity, apoptosis, neuroinflammation, neurodegeneration, and epilepsy.

    “miRs are well-established regulators of key brain processes 4,5 , including neurodevelopment [6][7][8][9][10][11] , synaptic plasticity [12][13][14] , apoptosis 15,16 , neuroinflammation 17 , neurodegeneration 18,19 , and epilepsy 5,20 .”

    From Human brain microRNAs exhibit cell-type specificity and age dependence (2026) · cites this paper as [4]

  • Primary neurons displayed high expression of miRNAs linked to neurological disorders such as epilepsy, including miR-129a, miR-134, miR-135a and miR-146a.

    “The primary neurons also displayed high expression of miRNAs linked to neurological disorders such as epilepsy, including miR-129a, miR-134, miR-135a and miR-146a [30].”

    From Shared and distinct microRNA profiles between HT22, N2A and SH-SY5Y cell lines and primary mouse hippocampal neurons (2025) · cites this paper as [30]

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Authors
Brennan, G. P., & Henshall, D. C.
ORCID
Henshall, David C.
Venue
Nature Reviews Neurology
Publisher
Springer Science and Business Media LLC
Published
2020-06-16
Volume
16
Issue
9
Pages
506-519
ISSN
  • 1759-4758
  • 1759-4766
DOI
10.1038/s41582-020-0369-8
Cited by
168
References
16
Language
en
Licence

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