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dc.contributor.authorDella-Flora Nunes, Gustavo
dc.contributor.authorWilson, Emma
dc.contributor.authorHurley, Edward
dc.contributor.authorHe, Bin
dc.contributor.authorO'Malley, Bert W
dc.contributor.authorPoitelon, Yannick
dc.contributor.authorWrabetz, Lawrence
dc.contributor.authorFeltri, M Laura
dc.date.accessioned2022-01-06T00:30:16Z
dc.date.available2022-01-06T00:30:16Z
dc.date.issued2021-09-14
dc.identifier.issn2050-084X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332107
dc.description.abstractSchwann cell (SC) mitochondria are quickly emerging as an important regulator of myelin maintenance in the peripheral nervous system (PNS). However, the mechanisms underlying demyelination in the context of mitochondrial dysfunction in the PNS are incompletely understood. We recently showed that conditional ablation of the mitochondrial protein Prohibitin 1 (PHB1) in SCs causes a severe and fast progressing demyelinating peripheral neuropathy in mice, but the mechanism that causes failure of myelin maintenance remained unknown. Here, we report that mTORC1 and c-Jun are continuously activated in the absence of Phb1, likely as part of the SC response to mitochondrial damage. Moreover, we demonstrate that these pathways are involved in the demyelination process, and that inhibition of mTORC1 using rapamycin partially rescues the demyelinating pathology. Therefore, we propose that mTORC1 and c-Jun may play a critical role as executioners of demyelination in the context of perturbations to SC mitochondria.
dc.format.mediumElectronic
dc.publishereLife Sciences Publications, Ltd
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectPHB1
dc.subjectdemyelination
dc.subjectmechanistic target of rapamycin
dc.subjectmitochondrial stress response
dc.subjectmouse
dc.subjectmyelin maintenance
dc.subjectneuroscience
dc.subjectschwann cells
dc.subjectAnimals
dc.subjectDemyelinating Diseases
dc.subjectMechanistic Target of Rapamycin Complex 1
dc.subjectMice
dc.subjectMice, Knockout
dc.subjectMitochondria
dc.subjectMyelin Sheath
dc.subjectProto-Oncogene Proteins c-jun
dc.subjectRepressor Proteins
dc.subjectSchwann Cells
dc.subjectUp-Regulation
dc.titleActivation of mTORC1 and c-Jun by Prohibitin1 loss in Schwann cells may link mitochondrial dysfunction to demyelination.
dc.typeArticle
dc.publisher.departmentDepartment of Clinical Neurosciences
dc.date.updated2021-12-09T14:48:41Z
prism.publicationDate2021
prism.publicationNameElife
prism.startingPagee66278
prism.volume10
dc.identifier.doi10.17863/CAM.79553
dcterms.dateAccepted2021-09-13
rioxxterms.versionofrecord10.7554/eLife.66278
rioxxterms.versionVoR
dc.contributor.orcidDella-Flora Nunes, Gustavo [0000-0001-9323-3556]
dc.contributor.orcidWilson, Emma [0000-0002-8069-0173]
dc.contributor.orcidHurley, Edward [0000-0002-1967-8933]
dc.contributor.orcidPoitelon, Yannick [0000-0001-9868-1569]
dc.contributor.orcidFeltri, M Laura [0000-0002-2276-9182]
dc.identifier.eissn2050-084X
rioxxterms.typeJournal Article/Review
cam.issuedOnline2021-09-14
cam.depositDate2021-12-09
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International