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dc.contributor.authorKappagantula, Sunil
dc.contributor.authorAndrews, Melissa Renee
dc.contributor.authorCheah, Menghon
dc.contributor.authorAbad-Rodriguez, Jose'
dc.contributor.authorDotti, Carlos G
dc.contributor.authorFawcett, James W
dc.date.accessioned2015-06-05T14:40:04Z
dc.date.available2015-06-05T14:40:04Z
dc.date.issued2014-02-12
dc.identifier.citationKappagantula , S , Andrews , M R , Cheah , M , Abad-Rodriguez , J , Dotti , C G & Fawcett , J W 2014 , ' Neu3 sialidase-mediated ganglioside conversion is necessary for axon regeneration and is blocked in CNS axons ' The Journal of Neuroscience , vol. 34 , no. 7 , pp. 2477-2492 . https://doi.org/10.1523/JNEUROSCI.4432-13.2014en
dc.identifier.issn0270-6474
dc.identifier.otherPURE: 96828247
dc.identifier.otherPURE UUID: 423e7858-6cdb-4cee-b86c-19ab9dedab27
dc.identifier.otherScopus: 84893665187
dc.identifier.urihttp://hdl.handle.net/10023/6767
dc.descriptionThis work was supported by the Medical Research Council, the Christopher and Dana Reeve Foundation, the John and Lucille van Geest Foundation, the Henry Smith Charity, the Commonwealth and Overseas scholarships, and the Hinduja Cambridge Trust.en
dc.description.abstractPNS axons have a high intrinsic regenerative ability, whereas most CNS axons show little regenerative response. We show that activation of Neu3 sialidase, also known as Neuraminidase-3, causing conversion of GD1a and GT1b to GM1 ganglioside, is an essential step in regeneration occurring in PNS (sensory) but not CNS (retinal) axons in adult rat. In PNS axons, axotomy activates Neu3 sialidase, increasing the ratio of GM1/GD1a and GM1/GT1b gangliosides immediately after injury in vitro and in vivo. No change in the GM1/GD1a ratio after axotomy was observed in retinal axons (in vitro and in vivo), despite the presence of Neu3 sialidase. Externally applied sialidase converted GD1a ganglioside to GM1 and rescued axon regeneration in CNS axons and in PNS axons after Neu3 sialidase blockade. Neu3 sialidase activation in DRGs is initiated by an influx of extracellular calcium, activating P38MAPK and then Neu3 sialidase. Ganglioside conversion by Neu3 sialidase further activates the ERK pathway. In CNS axons, P38MAPK and Neu3 sialidase were not activated by axotomy.
dc.language.isoeng
dc.relation.ispartofThe Journal of Neuroscienceen
dc.rightsCopyright © 2014 the authors. This is an article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for noncommercial use, provided the original work is properly citeden
dc.subjectAxon regenerationen
dc.subjectAxotomyen
dc.subjectGangliosidesen
dc.subjectNeu3 sialidaseen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.subject.lccRC0321en
dc.titleNeu3 sialidase-mediated ganglioside conversion is necessary for axon regeneration and is blocked in CNS axonsen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.identifier.doihttps://doi.org/10.1523/JNEUROSCI.4432-13.2014
dc.description.statusPeer revieweden


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