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Cited by 50Multiple Sclerosis Research StudiesNeurogenesis and neuroplasticity mechanismsNeuroinflammation and Neurodegeneration Mechanisms

Antibody-mediated neutralization of myelin-associated EphrinB3 accelerates CNS remyelination

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Syed, Yasir A., Zhao, Chao, Mahad, Don, Möbius, Wiebke, Altmann, Friedrich, Foss, Franziska, Sentürk, Aycan, Acker-Palmer, Amparo +5 more·2016·Acta Neuropathologica
DOI 10.1007/s00401-015-1521-1PMC PMC4713754
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Abstract

Remyelination in multiple sclerosis (MS) lesions often remains incomplete despite the presence of oligodendrocyte progenitor cells (OPCs). Amongst other factors, successful remyelination depends on the phagocytic clearance of myelin debris. However, the proteins in myelin debris that act as potent and selective inhibitors on OPC differentiation and inhibit CNS remyelination remain unknown. Here, we identify the transmembrane signalling protein EphrinB3 as important mediator of this inhibition, using a protein analytical approach in combination with a primary rodent OPC assay. In the presence of EphrinB3, OPCs fail to differentiate. In a rat model of remyelination, infusion of EphrinB3 inhibits remyelination. In contrast, masking EphrinB3 epitopes using antibodies promotes remyelination. Finally, we identify EphrinB3 in MS lesions and demonstrate that MS lesion extracts inhibit OPC differentiation while antibody-mediated masking of EphrinB3 epitopes promotes it. Our findings suggest that EphrinB3 could be a target for therapies aiming at promoting remyelination in demyelinating disease.

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Authors
Syed, Y. A., Zhao, C., Mahad, D., Möbius, W., Altmann, F., Foss, F., Sentürk, A., Acker-Palmer, A., Lubec, G., Lilley, K., Franklin, R. J. M., Nave, K.-A., & Kotter, M. R. N.
Affiliations
  • Wellcome/MRC Cambridge Stem Cell Institute (GB)
  • University of Edinburgh (GB)
  • Max Planck Institute of Experimental Medicine (DE)
  • BOKU University (AT)
  • Goethe University Frankfurt (DE)
  • University of Cambridge (GB)
Corresponding author
Kotter, Mark R. N.
ORCID
Venue
Acta Neuropathologica
Publisher
Springer Science and Business Media LLC
Published
2015-12-19
Volume
131
Issue
2
Pages
281-298
ISSN
  • 0001-6322 (ISSN-L)
  • 1432-0533
DOI
10.1007/s00401-015-1521-1
PMC
PMC4713754
OpenAlex
W2210658805
Cited by
50
References
8
Citations by year
2025: 2 · 2024: 8 · 2023: 3 · 2022: 4 · 2021: 11 · 2020: 2 · 2019: 6 · 2018: 5 · 2017: 6 · 2016: 3
FWCI
3.71
Type
journal article
Language
en
Update notices
Open access
Licence
Locations
  • Acta Neuropathologica (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion, cc-by)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
  • GRO (submittedVersion, cc-by)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
Funders
  • UK MS Society Grant (941/11)
  • European Research Council
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
ephrin-B3, remyelination, multiple sclerosis, oligodendrocyte precursor cells, OPC differentiation, myelin debris, antibody neutralization, demyelinating disease, myelin-associated inhibitors
MeSH terms
Animals, Epitopes, Cells, Cultured, Disease Models, Animal, Female, Humans, Macrophages, Multiple Sclerosis, Myelin Sheath, Nerve Regeneration, Oligodendroglia, Random Allocation, Rats, Sprague-Dawley, Mice, Knockout, Receptor, EphA4, Ephrin-B3, Neurogenesis, Neural Stem Cells

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