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dc.contributor.authorSmith, Nicholas Jcen
dc.contributor.authorFuller, Mariaen
dc.contributor.authorSaville, Jennifer Ten
dc.contributor.authorCox, Timothyen
dc.date.accessioned2018-01-17T16:23:24Z
dc.date.available2018-01-17T16:23:24Z
dc.date.issued2018-01en
dc.identifier.issn0022-3417
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/270706
dc.description.abstractABSTRACT The glycosphingolipidosis Gaucher disease, in which a range of neurological manifestations occur, results from a deficiency of acid β-glucocerebrosidase, with subsequent accumulation of β-glucocerebroside, its upstream substrates and the unacylated congener, ß-glucosylsphingosine. However, the mechanisms by which end-organ dysfunction arise are poorly understood. Here we report strikingly diminished cerebral microvascular density in a murine model of disease and provide a detailed analysis of the accompanying cerebral glycosphingolipidome in these animals, with marked elevations of ß-glucosylsphingosine. Further in vitro studies confirm a concentration dependent impairment of endothelial cytokinesis upon exposure to quasi-pathological concentrations of ß-glucosylsphingosine. These findings support a premise for pathogenic disruption of cerebral angiogenesis as an end-organ effect, with potential for therapeutic modulation in neuronopathic Gaucher disease.
dc.format.mediumPrinten
dc.languageengen
dc.publisherWiley-Blackwell
dc.subjectBrainen
dc.subjectAnimalsen
dc.subjectHumansen
dc.subjectMiceen
dc.subjectGaucher Diseaseen
dc.subjectDisease Models, Animalen
dc.subjectNeovascularization, Pathologicen
dc.subjectPsychosineen
dc.subjectMicrovesselsen
dc.titleReduced cerebral vascularization in experimental neuronopathic Gaucher disease.en
dc.typeArticle
prism.endingPage128
prism.issueIdentifier1en
prism.publicationDate2018en
prism.publicationNameThe Journal of pathologyen
prism.startingPage120
prism.volume244en
dc.identifier.doi10.17863/CAM.17644
dcterms.dateAccepted2017-09-12en
rioxxterms.versionofrecord10.1002/path.4992en
rioxxterms.versionAM*
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-01en
dc.contributor.orcidSmith, Nicholas Jc [0000-0003-2409-9239]
dc.contributor.orcidCox, Timothy [0000-0002-4951-9941]
dc.identifier.eissn1096-9896
rioxxterms.typeJournal Article/Reviewen
rioxxterms.freetoread.startdate2018-10-05


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