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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Autores: Wagstaff LJ, Gomez-Sanchez JA, Fazal SV, Otto GW, Kilpatrick AM, Michael K, Wong LYN, Ma KH, Turmaine M, Svaren J, Gordon T, Arthur-Farraj P, Velasco-Aviles S, Cabedo H, Benito C, Mirsky R, Jessen KR
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
Repositorio:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
OAI Identifier:oai:isabial.fundanetsuite.com:p6459
Acceso en línea:https://isabial.portalinvestigacion.com/publicaciones6459
Access Level:acceso abierto
Palabra clave:*aging
*c-Jun
*chronic denervation
*mouse
*nerve regeneration
*neuroscience
*regenerative medicine
*repair cell
*schwann cell
*stem cells
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spelling Failures of nerve regeneration caused by aging or chronic denervation are rescued by restoring Schwann cell c-Jun.Wagstaff LJGomez-Sanchez JAFazal SVOtto GWKilpatrick AMMichael KWong LYNMa KHTurmaine MSvaren JGordon TArthur-Farraj PVelasco-Aviles SCabedo HBenito CMirsky RJessen KR*aging*c-Jun*chronic denervation*mouse*nerve regeneration*neuroscience*regenerative medicine*repair cell*schwann cell*stem cellsAfter 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.eLIFE SCIENCES PUBL LTD2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://isabial.portalinvestigacion.com/publicaciones6459eLifeISSN: 2050084Xreponame:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicanteinstname:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)Inglésinfo:eu-repo/semantics/openAccessoai:isabial.fundanetsuite.com:p64592026-06-12T10:20:37Z
dc.title.none.fl_str_mv Failures of nerve regeneration caused by aging or chronic denervation are rescued by restoring Schwann cell c-Jun.
title Failures of nerve regeneration caused by aging or chronic denervation are rescued by restoring Schwann cell c-Jun.
spellingShingle Failures of nerve regeneration caused by aging or chronic denervation are rescued by restoring Schwann cell c-Jun.
Wagstaff LJ
*aging
*c-Jun
*chronic denervation
*mouse
*nerve regeneration
*neuroscience
*regenerative medicine
*repair cell
*schwann cell
*stem cells
title_short Failures of nerve regeneration caused by aging or chronic denervation are rescued by restoring Schwann cell c-Jun.
title_full Failures of nerve regeneration caused by aging or chronic denervation are rescued by restoring Schwann cell c-Jun.
title_fullStr Failures of nerve regeneration caused by aging or chronic denervation are rescued by restoring Schwann cell c-Jun.
title_full_unstemmed Failures of nerve regeneration caused by aging or chronic denervation are rescued by restoring Schwann cell c-Jun.
title_sort Failures of nerve regeneration caused by aging or chronic denervation are rescued by restoring Schwann cell c-Jun.
dc.creator.none.fl_str_mv Wagstaff LJ
Gomez-Sanchez JA
Fazal SV
Otto GW
Kilpatrick AM
Michael K
Wong LYN
Ma KH
Turmaine M
Svaren J
Gordon T
Arthur-Farraj P
Velasco-Aviles S
Cabedo H
Benito C
Mirsky R
Jessen KR
author Wagstaff LJ
author_facet Wagstaff LJ
Gomez-Sanchez JA
Fazal SV
Otto GW
Kilpatrick AM
Michael K
Wong LYN
Ma KH
Turmaine M
Svaren J
Gordon T
Arthur-Farraj P
Velasco-Aviles S
Cabedo H
Benito C
Mirsky R
Jessen KR
author_role author
author2 Gomez-Sanchez JA
Fazal SV
Otto GW
Kilpatrick AM
Michael K
Wong LYN
Ma KH
Turmaine M
Svaren J
Gordon T
Arthur-Farraj P
Velasco-Aviles S
Cabedo H
Benito C
Mirsky R
Jessen KR
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv *aging
*c-Jun
*chronic denervation
*mouse
*nerve regeneration
*neuroscience
*regenerative medicine
*repair cell
*schwann cell
*stem cells
topic *aging
*c-Jun
*chronic denervation
*mouse
*nerve regeneration
*neuroscience
*regenerative medicine
*repair cell
*schwann cell
*stem cells
description 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.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://isabial.portalinvestigacion.com/publicaciones6459
url https://isabial.portalinvestigacion.com/publicaciones6459
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv eLIFE SCIENCES PUBL LTD
publisher.none.fl_str_mv eLIFE SCIENCES PUBL LTD
dc.source.none.fl_str_mv eLife
ISSN: 2050084X
reponame:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
instname:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
instname_str Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
reponame_str r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
collection r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.81155

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