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Authordc.contributor.authorOñate, Martiza 
Authordc.contributor.authorCatenaccio, Alejandra 
Authordc.contributor.authorMartínez, Gabriela 
Authordc.contributor.authorArmentano, Donna 
Authordc.contributor.authorParsons, Geoffrey 
Authordc.contributor.authorKerr, Bredford 
Authordc.contributor.authorHetz Flores, Claudio 
Authordc.contributor.authorCourt, Felipe 
Cita de ítemdc.identifier.citationScientific Reports | 6:21709 | 2016en_US
Identifierdc.identifier.otherDOI: 10.1038/srep21709
General notedc.descriptionArtículo de publicación ISIen_US
Abstractdc.description.abstractAlthough protein-folding stress at the endoplasmic reticulum (ER) is emerging as a driver of neuronal dysfunction in models of spinal cord injury and neurodegeneration, the contribution of this pathway to peripheral nerve damage remains poorly explored. Here we targeted the unfolded protein response (UPR), an adaptive reaction against ER stress, in mouse models of sciatic nerve injury and found that ablation of the transcription factor XBP1, but not ATF4, significantly delay locomotor recovery. XBP1 deficiency led to decreased macrophage recruitment, a reduction in myelin removal and axonal regeneration. Conversely, overexpression of XBP1s in the nervous system in transgenic mice enhanced locomotor recovery after sciatic nerve crush, associated to an improvement in key pro-regenerative events. To assess the therapeutic potential of UPR manipulation to axonal regeneration, we locally delivered XBP1s or an shRNA targeting this transcription factor to sensory neurons of the dorsal root ganglia using a gene therapy approach and found an enhancement or reduction of axonal regeneration in vivo, respectively. Our results demonstrate a functional role of specific components of the ER proteostasis network in the cellular changes associated to regeneration and functional recovery after peripheral nerve injury.en_US
Patrocinadordc.description.sponsorshipMillennium Nucleus P-07-011-F FONDECYT 1110987 1140549 3150637 Ring Initiative ACT1109 Millennium Institute P09-015-F Frick Foundation Michael J Fox Foundation for Parkinson's Research COPEC-UC Foundation CONICYT-USA 2013-0003 ECOS-CONICYT C13S02 Muscular Dystrophy Association 382453 ALS Therapy Alliance 2014-F-059 Office of Naval Research-Global (ONR-G) N62909-16-1-2003 ALSRP Therapeutic Idea Award AL150111 Centers of Excellence Basal Financing Program of CONICYT CONICYT FONDAP-15150012en_US
Publisherdc.publisherNature Publishing Groupen_US
Type of licensedc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile*
Link to Licensedc.rights.uri*
Títulodc.titleActivation of the unfolded protein response promotes axonal regeneration after peripheral nerve injuryen_US
Document typedc.typeArtículo de revista

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Atribución-NoComercial-SinDerivadas 3.0 Chile
Except where otherwise noted, this item's license is described as Atribución-NoComercial-SinDerivadas 3.0 Chile