Next Article in Journal
ApoA-I-Mediated Lipoprotein Remodeling Monitored with a Fluorescent Phospholipid
Previous Article in Journal
Curcumin Regulates Anti-Inflammatory Responses by JAK/STAT/SOCS Signaling Pathway in BV-2 Microglial Cells
Article Menu

Export Article

Open AccessArticle

The Use of Myelinating Cultures as a Screen of Glycomolecules for CNS Repair

1
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK
2
GlycoMar Limited, Malin House, European Marine Science Park, Dunbeg, Oban Argyll, Scotland PA37 1SZ, UK
*
Author to whom correspondence should be addressed.
Biology 2019, 8(3), 52; https://doi.org/10.3390/biology8030052
Received: 25 April 2019 / Revised: 11 June 2019 / Accepted: 21 June 2019 / Published: 28 June 2019
(This article belongs to the Special Issue Models of CNS Regeneration: Mind the Gap!)
  |  
PDF [4979 KB, uploaded 28 June 2019]
  |  

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. View Full-Text
Keywords: myelination; neurite outgrowth; cell culture; heparin sulphate; moderate throughput screen myelination; neurite outgrowth; cell culture; heparin sulphate; moderate throughput screen
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

McCanney, G.A.; Lindsay, S.L.; McGrath, M.A.; Willison, H.J.; Moss, C.; Bavington, C.; Barnett, S.C. The Use of Myelinating Cultures as a Screen of Glycomolecules for CNS Repair. Biology 2019, 8, 52.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Biology EISSN 2079-7737 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top