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dc.contributor.authorHill, Ciaran
dc.contributor.authorMenon, David
dc.contributor.authorColeman, MP
dc.date.accessioned2018-12-04T00:31:15Z
dc.date.available2018-12-04T00:31:15Z
dc.date.issued2018-12-12
dc.identifier.issn0959-4965
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/286268
dc.description.abstractThe anti-apoptotic, neuroprotective compound P7C3-A20 reduces neurological deficits when administered to murine in vivo models of traumatic brain injury. P7C3-A20 is thought to exert its activity through small-molecule activation of the enzyme nicotinamide phosphoribosyltransferase (NAMPT). This enzyme converts nicotinamide to nicotinamide mononucleotide (NMN), the precursor to nicotinamide adenine dinucleotide (NAD) synthesis. Alterations to this bioenergetic pathway have been shown to induce Wallerian degeneration of the distal neurite following injury. This study aimed to establish whether P7C3-A20, through induction of NAMPT activity, would affect the rate of Wallerian degeneration. The model systems used were dissociated primary cortical neurons, dissociated superior cervical ganglion neurons, and superior cervical ganglion explants. P7C3-A20 failed to demonstrate any protection against Wallerian degeneration induced by neurite transection or vincristine administration. Furthermore, there was a concentration dependent neurotoxicity. These findings are important in understanding the mechanism by which P7C3-A20 mediates its effects- a key step before moving to human clinical trials.
dc.description.sponsorshipWellcome Trust
dc.publisherWolters Kluwer Health
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleP7C3-A20 neuroprotection is independent of Wallerian degeneration in Primary Neuronal Culture
dc.typeArticle
prism.publicationNameNeuroReport
dc.identifier.doi10.17863/CAM.33580
dcterms.dateAccepted2018-09-21
rioxxterms.versionofrecord10.1097/WNR.0000000000001146
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-09-21
dc.contributor.orcidMenon, David [0000-0002-3228-9692]
dc.contributor.orcidColeman, Michael [0000-0002-9354-532X]
dc.identifier.eissn1473-558X
rioxxterms.typeJournal Article/Review
pubs.funder-project-idEuropean Commission (602150)
cam.issuedOnline2018-10-17
cam.orpheus.successThu Jan 30 10:53:51 GMT 2020 - The item has an open VoR version.
rioxxterms.freetoread.startdate2100-01-01


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