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Inhibition of CNS remyelination by the presence of semaphorin 3A

Syed, Yasir A., Hand, E., Mobius, W., Zhao, C., Hofer, M., Nave, K. A. and Kotter, M. R. 2011. Inhibition of CNS remyelination by the presence of semaphorin 3A. Journal of Neuroscience 31 (10) , pp. 3719-3728. 10.1523/JNEUROSCI.4930-10.2011

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Abstract

Failure of oligodendrocyteprecursor cell (OPC)differentiationhasbeen recognized asthe leading causeforthefailure ofmyelin regenerationin diseases such as multiple sclerosis (MS). One explanation for the failure of OPC differentiation in MS is the presence of inhibitory molecules in demyelinatedlesions.Sofaronly afewinhibitory substrateshavebeenidentifiedinMSlesions.Semaphorin3A (Sema3A), a secretedmemberof the semaphorin family, can act as repulsive guidance cue for neuronal and glial cells in the CNS. Recent studies suggest that Sema3A is also expressedin activeMSlesions.However,theimplicationof Sema3A expressioninMSlesions remainsunclear asOPCs are commonlypresentin 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Society for Neuroscience
ISSN: 0270-6474
Date of First Compliant Deposit: 21 February 2017
Date of Acceptance: 27 October 2010
Last Modified: 04 Jun 2017 09:43
URI: http://orca.cf.ac.uk/id/eprint/98440

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