Whitehead, M. J., McGonigal, R. , Willison, H. J. and Barnett, S. C. (2018) Heparanase attenuates axon degeneration following sciatic nerve transection. Scientific Reports, 8, 5219. (doi: 10.1038/s41598-018-23070-6) (PMID:29581478) (PMCID:PMC5980233)
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Abstract
Axon degeneration underlies many nervous system diseases; therefore understanding the regulatory signalling pathways is fundamental to identifying potential therapeutics. Previously, we demonstrated heparan sulphates (HS) as a potentially new target for promoting CNS repair. HS modulate cell signalling by both acting as cofactors in the formation of ligand-receptor complexes and in sequestering ligands in the extracellular matrix. The enzyme heparanase (Hpse) negatively regulates these processes by cleaving HS and releasing the attached proteins, thereby attenuating their ligand-receptor interaction. To explore a comparative role for HS in PNS axon injury/repair we data mined published microarrays from distal sciatic nerve injury. We identified Hpse as a previously unexplored candidate, being up-regulated following injury. We confirmed these results and demonstrated inhibition of Hpse led to an acceleration of axonal degeneration, accompanied by an increase in β-catenin. Inhibition of β-catenin and the addition of Heparinase I both attenuated axonal degeneration. Furthermore the inhibition of Hpse positively regulates transcription of genes associated with peripheral neuropathies and Schwann cell de-differentiation. Thus, we propose Hpse participates in the regulation of the Schwann cell injury response and axo-glia support, in part via the regulation of Schwann cell de-differentiation and is a potential therapeutic that warrants further investigation.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Willison, Professor Hugh and Barnett, Professor Susan and McGonigal, Dr Rhona and Whitehead, Mr Michael |
| Authors: | Whitehead, M. J., McGonigal, R., Willison, H. J., and Barnett, S. C. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Scientific Reports |
| Publisher: | Nature Publishing Group |
| ISSN: | 2045-2322 |
| ISSN (Online): | 2045-2322 |
| Copyright Holders: | Copyright © 2018 The Authors |
| First Published: | First published in Scientific Reports 8:5219 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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