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Inhibition of CNS Remyelination by the Presence of Semaphorin 3A
Open accessAbstract
Failure of oligodendrocyte precursor cell (OPC) differentiation has been recognized as the leading cause for the failure of myelin regeneration in diseases such as multiple sclerosis (MS). One explanation for the failure of OPC differentiation in MS is the presence of inhibitory molecules in demyelinated lesions. So far only a few inhibitory substrates have been identified in MS lesions. Semaphorin 3A (Sema3A), a secreted member of the semaphorin family, can act as repulsive guidance cue for neuronal and glial cells in the CNS. Recent studies suggest that Sema3A is also expressed in active MS lesions. However, the implication of Sema3A expression in MS lesions remains unclear as OPCs are commonly present in chronic demyelinated lesions. In the present study we identify Sema3A as a potent, selective, and reversible inhibitor of OPC differentiation in vitro. Furthermore, we show that administration of Sema3A into demyelinating lesions in the rat CNS results in a failure of remyelination. Our results imply an important role for Sema3A in the differentiation block occurring in MS lesions.
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“Since the efficiency of remyelination is inversely correlated with lesion size, this model is advantageous for studying the kinetics of CNS remyelination36.”
From Tamoxifen accelerates the repair of demyelinated lesions in the central nervous system (2016) · cites this paper as [36]
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Metadata
- Authors
- Syed, Y. A., Hand, E., Möbius, W., Zhao, C., Hofer, M., Nave, K. A., & Kotter, M. R.
- Affiliations
- University of Cambridge (GB)
- Max Planck Society (DE)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-03-09
- Volume
- 31
- Issue
- 10
- Pages
- 3719-3728
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6622776
- OpenAlex
- W2000180092
- Cited by
- 134
- References
- 61
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 8 · 2023: 8 · 2022: 4 · 2021: 9 · 2020: 5 · 2019: 10 · 2018: 5 · 2017: 11 · 2016: 10 · 2015: 18 · 2014: 13 · 2013: 9 · 2012: 9
- FWCI
- 8.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- semaphorin 3A, remyelination, oligodendrocyte precursor cells, oligodendrocyte differentiation, multiple sclerosis, demyelination, inhibitory molecules, demyelinating lesions
- MeSH terms
- Analysis of Variance, Animals, Animals, Newborn, Cell Differentiation, Female, Immunohistochemistry, Myelin Sheath, Nerve Regeneration, Oligodendroglia, Rats, Sprague-Dawley, In Situ Hybridization, Reverse Transcriptase Polymerase Chain Reaction, Semaphorin-3A, Rats
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