Failures of nerve regeneration caused by aging or chronic denervation are rescued by restoring Schwann cell c-Jun
After nerve injury, myelin and Remak Schwann cells reprogram to repair cells specialized for regeneration. Normally providing strong regenerative support, these cells fail in aging animals, and during chronic denervation that results from slow axon growth. This impairs axonal regeneration and causes...
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Published in | eLife Vol. 10 |
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Main Authors | , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
eLife Sciences Publications Ltd
21.01.2021
eLife Sciences Publications, Ltd |
Subjects | |
Online Access | Get full text |
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Summary: | After nerve injury, myelin and Remak Schwann cells reprogram to repair cells specialized for regeneration. Normally providing strong regenerative support, these cells fail in aging animals, and during chronic denervation that results from slow axon growth. This impairs axonal regeneration and causes significant clinical problems. In mice, we find that repair cells express reduced c-Jun protein as regenerative support provided by these cells declines during aging and chronic denervation. In both cases, genetically restoring Schwann cell c-Jun levels restores regeneration to control levels. We identify potential gene candidates mediating this effect and implicate Shh in the control of Schwann cell c-Jun levels. This establishes that a common mechanism, reduced c-Jun in Schwann cells, regulates success and failure of nerve repair both during aging and chronic denervation. This provides a molecular framework for addressing important clinical problems, suggesting molecular pathways that can be targeted to promote repair in the PNS. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Centre for Regenerative Medicine, Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh BioQuarter,5 Little France Drive, Edinburgh, United Kingdom. These authors contributed equally to this work. John Van Geest Centre for Brian Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom. |
ISSN: | 2050-084X 2050-084X |
DOI: | 10.7554/eLife.62232 |