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dc.contributor.authorCoppa, Andrea
dc.contributor.authorGuha, Sanjib
dc.contributor.authorFourcade, Stéphane
dc.contributor.authorParameswaran, Janani
dc.contributor.authorRuiz, Montserrat
dc.contributor.authorMoser, Ann B
dc.contributor.authorSchlüter, Agatha
dc.contributor.authorMurphy, Michael P
dc.contributor.authorLizcano, Jose Miguel
dc.contributor.authorMiranda-Vizuete, Antonio
dc.contributor.authorDalfó, Esther
dc.contributor.authorPujol, Aurora
dc.date.accessioned2020-02-18T05:28:06Z
dc.date.available2020-02-18T05:28:06Z
dc.date.issued2020-05-20
dc.identifier.issn0891-5849
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/302316
dc.description.abstractAdrenoleukodystrophy is a neurometabolic disorder caused by a defective peroxisomal ABCD1 transporter of very long-chain fatty acids (VLCFAs). Its pathogenesis is incompletely understood. Here we characterize a nematode model of X-ALD with loss of the pmp-4 gene, the worm orthologue of ABCD1. These mutants recapitulate the hallmarks of X-ALD: i) VLCFAs accumulation and impaired mitochondrial redox homeostasis and ii) axonal damage coupled to locomotor dysfunction. Furthermore, we identify a novel role for PMP-4 in modulating lipid droplet dynamics. Importantly, we show that the mitochondria targeted antioxidant MitoQ normalizes lipid droplets size, and prevents axonal degeneration and locomotor disability, highlighting its therapeutic potential. Moreover, PMP-4 acting solely in the hypodermis rescues axonal and locomotion abnormalities, suggesting a myelin-like role for the hypodermis in providing essential peroxisomal functions for the nematode nervous system.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherElsevier BV
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectSubcutaneous Tissue
dc.subjectAnimals
dc.subjectMice, Knockout
dc.subjectMice
dc.subjectCaenorhabditis elegans
dc.subjectAdrenoleukodystrophy
dc.subjectFatty Acids
dc.subjectATP-Binding Cassette Transporters
dc.subjectATP Binding Cassette Transporter, Subfamily D, Member 1
dc.titleThe peroxisomal fatty acid transporter ABCD1/PMP-4 is required in the C. elegans hypodermis for axonal maintenance: A worm model for adrenoleukodystrophy.
dc.typeArticle
prism.endingPage809
prism.publicationDate2020
prism.publicationNameFree Radic Biol Med
prism.startingPage797
prism.volume152
dc.identifier.doi10.17863/CAM.49389
dcterms.dateAccepted2020-01-20
rioxxterms.versionofrecord10.1016/j.freeradbiomed.2020.01.177
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2020-05
dc.contributor.orcidMurphy, Mike [0000-0003-1115-9618]
dc.identifier.eissn1873-4596
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MC_UU_00015/3)
pubs.funder-project-idWellcome Trust (110159/Z/15/Z)
cam.issuedOnline2020-02
cam.orpheus.successTue Mar 31 10:36:10 BST 2020 - Embargo updated
rioxxterms.freetoread.startdate2021-02-28


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