Failures of nerve regeneration caused by aging or chronic denervation are rescued by restoring Schwann cell c-Jun.
aging
c-Jun
chronic denervation
mouse
nerve regeneration
neuroscience
regenerative medicine
repair cell
schwann cell
stem cells
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
21 01 2021
21 01 2021
Historique:
received:
18
08
2020
accepted:
21
12
2020
entrez:
21
1
2021
pubmed:
22
1
2021
medline:
2
2
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33475496
doi: 10.7554/eLife.62232
pii: 62232
pmc: PMC7819709
doi:
pii:
Substances chimiques
Proto-Oncogene Proteins c-jun
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wellcome Trust
ID : PhD studentship 511851 FBAGG F96 WT Stern (No 161 761
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206634
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 074665
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206634/Z/17/Z
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : NS075269
Pays : United States
Organisme : National Institute of Child Health and Human Development
ID : HD090256
Organisme : NINDS NIH HHS
ID : R01 NS100510
Pays : United States
Organisme : Medical Research Council
ID : MR/K017047/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0600967
Pays : United Kingdom
Informations de copyright
© 2021, Wagstaff et al.
Déclaration de conflit d'intérêts
LW, JG, SF, GO, AK, KM, LW, KM, MT, JS, TG, PA, SV, HC, CB, RM, KJ No competing interests declared
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