Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

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) 10.1007/s00401-015-1521-1

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (4MB) | Preview

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Uncontrolled Keywords: Remyelination; EphrinB3; Oligodendrocytes; Multiple sclerosis
Publisher: Springer Verlag (Germany)
ISSN: 0001-6322
Date of First Compliant Deposit: 14 February 2017
Date of Acceptance: 6 December 2015
Last Modified: 07 Apr 2020 09:00
URI: http://orca.cf.ac.uk/id/eprint/98202

Citation Data

Cited 11 times in Google Scholar. View in Google Scholar

Cited 20 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics