MicroRNA-92a–CPEB3 axis protects neurons against inflammatory neurodegeneration
Open accessAbstract
Neuroinflammation causes neuronal injury in multiple sclerosis (MS) and other neurological diseases. MicroRNAs (miRNAs) are important modulators of neuronal stress responses, but knowledge about their contribution to neuronal protection or damage during inflammation is limited. Here, we constructed a regulatory miRNA–mRNA network of inflamed motor neurons by leveraging cell type–specific miRNA and mRNA sequencing of mice undergoing experimental autoimmune encephalomyelitis (EAE). We found robust induction of miR-92a in inflamed spinal cord neurons and identified cytoplasmic polyadenylation element-binding protein 3 ( Cpeb3 ) as a key target of miR-92a–mediated posttranscriptional silencing. We detected CPEB3 repression in inflamed neurons in murine EAE and human MS. Moreover, both miR-92a delivery and Cpeb3 deletion protected neuronal cultures against excitotoxicity. Supporting a detrimental effect of Cpeb3 in vivo, neuron-specific deletion in conditional Cpeb3 knockout animals led to reduced inflammation-induced clinical disability in EAE. Together, we identified a neuroprotective miR-92a– Cpeb3 axis in neuroinflammation that might serve as potential treatment target to limit inflammation-induced neuronal damage.
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- Authors
- Winkler, I., Engler, J. B., Vieira, V., Bauer, S., Liu, Y.-H., Di Liberto, G., Grochowska, K. M., Wagner, I., Bier, J., Bal, L. C., Rothammer, N., Meurs, N., Egervari, K., Schattling, B., Salinas, G., Kreutz, M. R., Huang, Y.-S., Pless, O., Merkler, D., & Friese, M. A.
- Affiliations
- University Medical Center Hamburg-Eppendorf (DE)
- Institute of Biomedical Sciences, Academia Sinica (TW)
- Department of Pathology and Immunology, Division of Clinical Pathology, Geneva Faculty of Medicine, University of Geneva and University Hospital of Geneva, Geneva 1211, Switzerland.
- University of Geneva (CH)
- Universitätsmedizin Göttingen (DE)
- Fraunhofer Institute for Translational Medicine and Pharmacology (DE)
- Corresponding author
- Friese, Manuel A.
- ORCID
- Winkler, Iris
- Engler, Jan Broder
- Vieira, Vanessa
- Bauer, Simone
- Liu, Yi-Hsiang
- Di Liberto, Giovanni
- Grochowska, Katarzyna M.
- Wagner, Ingrid
- Bier, Jasmina
- Bal, Lukas C.
- Rothammer, Nicola
- Meurs, Nina
- Egervari, Kristof
- Schattling, Benjamin
- Salinas, Gabriela
- Kreutz, Michael R.
- Huang, Yi-Shuian
- Pless, Ole
- Merkler, Doron
- Friese, Manuel A.
- Venue
- Science Advances
- Published
- 2023-11-24
- Volume
- 9
- Issue
- 47
- Pages
- eadi6855-eadi6855
- ISSN
- 2375-2548 (ISSN-L)
- PMC
- PMC10672163
- OpenAlex
- W4388966688
- Cited by
- 22
- References
- 58
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 5
- FWCI
- 3.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
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- cc-by
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- PubMed Central (publishedVersion, cc-by)
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- Archive ouverte UNIGE (University of Geneva) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- microRNA-92a, CPEB3, neuroinflammation, neuroprotection, multiple sclerosis, experimental autoimmune encephalomyelitis, motor neurons, post-transcriptional gene silencing, excitotoxicity, spinal cord, neuronal injury, miRNA-mRNA regulatory network, conditional knockout
- MeSH terms
- Neuroinflammatory Diseases, Animals, Encephalomyelitis, Autoimmune, Experimental, Humans, Inflammation, Mice, Inbred C57BL, Multiple Sclerosis, Neurons, RNA, Messenger, RNA-Binding Proteins, MicroRNAs, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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