The use of myelinating cultures as a screen of glycomolecules for CNS repair

McCanney, G. A., Lindsay, S. L., McGrath, M. A., Willison, H. , Moss, C., Bavington, C. and Barnett, S. C. (2019) The use of myelinating cultures as a screen of glycomolecules for CNS repair. Biology, 8(3), 52. (doi: 10.3390/biology8030052) (PMID:31261710)

[img]
Preview
Text
185300.pdf - Published Version
Available under License Creative Commons Attribution.

5MB

Abstract

In vitro cell-based assays have been fundamental in modern drug discovery and have led to the identification of novel therapeutics. We have developed complex mixed central nervous system (CNS) cultures, which recapitulate the normal process of myelination over time and allow the study of several parameters associated with CNS damage, both during development and after injury or disease. In particular, they have been used as a reliable screen to identify drug candidates that may promote (re)myelination and/or neurite outgrowth. Previously, using these cultures, we demonstrated that a panel of low sulphated heparin mimetics, with structures similar to heparan sulphates (HSs), can reduce astrogliosis, and promote myelination and neurite outgrowth. HSs reside in either the extracellular matrix or on the surface of cells and are thought to modulate cell signaling by both sequestering ligands, and acting as co-factors in the formation of ligand-receptor complexes. In this study, we have used these cultures as a screen to address the repair potential of numerous other commercially available sulphated glycomolecules, namely heparosans, ulvans, and fucoidans. These compounds are all known to have certain characteristics that mimic cellular glycosaminoglycans, similar to heparin mimetics. We show that the N-sulphated heparosans promoted myelination. However, O-sulphated heparosans did not affect myelination but promoted neurite outgrowth, indicating the importance of structure in HS function. Moreover, neither highly sulphated ulvans nor fucoidans had any effect on remyelination but CX-01, a low sulphated porcine intestinal heparin, promoted remyelination in vitro. These data illustrate the use of myelinating cultures as a screen and demonstrate the potential of heparin mimetics as CNS therapeutics.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Willison, Professor Hugh and Barnett, Professor Susan and Mcgrath, Mr Michael and Lindsay, Dr Susan and McCanney, George
Authors: McCanney, G. A., Lindsay, S. L., McGrath, M. A., Willison, H., Moss, C., Bavington, C., and Barnett, S. C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Biology
Publisher:MDPI
ISSN:2079-7737
ISSN (Online):2079-7737
Published Online:28 June 2019
Copyright Holders:Copyright © 2019 by the authors
First Published:First published in Biology 8(3):52
Publisher Policy:Reproduced under a Creative Commons license

University Staff: Request a correction | Enlighten Editors: Update this record