Cited by 117Neurogenesis and neuroplasticity mechanismsMicroRNA in disease regulationMultiple Sclerosis Research Studies

MicroRNA-23a promotes myelination in the central nervous system

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Lin, Shu-Ting, Huang, Yong, Zhang, Luoying, Heng, Mary Y., Ptáček, Louis J., Fu, Ying-Hui·2013·Proceedings of the National Academy of Sciences

Abstract

Demyelinating disorders including leukodystrophies are devastating conditions that are still in need of better understanding, and both oligodendrocyte differentiation and myelin synthesis pathways are potential avenues for developing treatment. Overexpression of lamin B1 leads to leukodystrophy characterized by demyelination of the central nervous system, and microRNA-23 (miR-23) was found to suppress lamin B1 and enhance oligodendrocyte differentiation in vitro. Here, we demonstrated that miR-23a-overexpressing mice have increased myelin thickness, providing in vivo evidence that miR-23a enhances both oligodendrocyte differentiation and myelin synthesis. Using this mouse model, we explored possible miR-23a targets and revealed that the phosphatase and tensin homologue/phosphatidylinositol trisphosphate kinase/Akt/mammalian target of rapamycin pathway is modulated by miR-23a. Additionally, a long noncoding RNA, 2700046G09Rik, was identified as a miR-23a target and modulates phosphatase and tensin homologue itself in a miR-23a-dependent manner. The data presented here imply a unique role for miR-23a in the coordination of proteins and noncoding RNAs in generating and maintaining healthy myelin.

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  • miR-23a can inhibit expression of lamin B1 to protect against leukodystrophy characterized by demyelination of the central nervous system.

    “it can inhibit the expression of lamin B1 to protect against leukodystrophy characterized by demyelination of the central nervous system.”

    From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [134]

    The paper identifies lamin B1 as a target of miR-23a and links excess lamin B1 to leukodystrophy with central nervous system demyelination. However, the Discussion presents protection against demyelinating disease as a possible future therapeutic application, not a demonstrated effect of miR-23a. (LLM, conf=0.87)

    Experimental — accuracy not yet measured
  • LncRNA 2700046G09Rik was targeted by miR-23a to modulate PTEN and maintain normal myelin function.

    “LncRNA 2700046G09Rik was targeted by miR-23a to modulate phosphatase and tensin homolog and maintain normal myelin function [133,134].”
  • Overexpressing miR-23a in mice was observed as the thickness of myelin increases.

    “overexpressing miR-23a in mice was observed as the thickness of myelin increases”

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  1. Qi Y, et al. (2001) Control of oligodendrocyte differentiation by the Nkx2.2 homeo- domain transcription factor. Development 128(14):2723-2733.

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Authors
Lin, S.-T., Huang, Y., Zhang, L., Heng, M. Y., Ptáček, L. J., & Fu, Y.-H.
Affiliations
  • Department of Neurology and
  • Howard Hughes Medical Institute (US)
Venue
Proceedings of the National Academy of Sciences
Published
2013-10-07
Volume
110
Issue
43
Pages
17468-17473
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2071512787
Cited by
117
References
39
Citations by year
2026: 8 · 2025: 3 · 2024: 10 · 2023: 9 · 2022: 7 · 2021: 9 · 2020: 13 · 2019: 20 · 2018: 3 · 2017: 9 · 2016: 9 · 2015: 9 · 2014: 8
FWCI
3.22
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK063720)
  • National Institute of Neurological Disorders and Stroke (NS062733, R01NS062733)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
Keywords
microRNA-23a, myelination, oligodendrocyte differentiation, lamin B1, leukodystrophy, demyelination, myelin synthesis, microRNA target regulation, central nervous system
MeSH terms
Animals, Cell Differentiation, Cells, Cultured, Central Nervous System, Humans, Mice, Inbred C57BL, Mice, Transgenic, Microscopy, Electron, Myelin Sheath, Oligodendroglia, Blotting, Western, Signal Transduction, Reverse Transcriptase Polymerase Chain Reaction, MicroRNAs, Proto-Oncogene Proteins c-akt, PTEN Phosphohydrolase, Mice, HEK293 Cells, TOR Serine-Threonine Kinases, Transcriptome, RNA, Long Noncoding

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