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

Syed, Yasir A., Zhao, Chao, Mahad, Don, Möbius, Wiebke, Altmann, Friedrich, Foss, Franziska, Sentürk, Aycan, Acker-Palmer, Amparo, Lubec, Gert, Lilley, Kathryn, Franklin, Robin J. M., Nave, Klaus-A. and Kotter, Mark R. N. 2016. Antibody-mediated neutralization of myelin-associated EphrinB3 accelerates CNS remyelination. Acta Neuropathologica 131 (2) , pp. 281-298. 10.1007/s00401-015-1521-1

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Uncontrolled Keywords: Remyelination; EphrinB3; Oligodendrocytes; Multiple sclerosis
Additional Information: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License.
Publisher: Springer Verlag
ISSN: 0001-6322
Date of First Compliant Deposit: 14 February 2017
Date of Acceptance: 6 December 2015
Last Modified: 16 Nov 2020 10:45

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