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dc.contributor.authorSchöndorf, David Cen
dc.contributor.authorIvanyuk, Dinaen
dc.contributor.authorBaden, Pascaleen
dc.contributor.authorSanchez-Martinez, Alvaroen
dc.contributor.authorDe Cicco, Silviaen
dc.contributor.authorYu, Congen
dc.contributor.authorGiunta, Ivanaen
dc.contributor.authorSchwarz, Lukas Ken
dc.contributor.authorDi Napoli, Gabrieleen
dc.contributor.authorPanagiotakopoulou, Vasilikien
dc.contributor.authorNestel, Sigrunen
dc.contributor.authorKeatinge, Marcusen
dc.contributor.authorPruszak, Janen
dc.contributor.authorBandmann, Oliveren
dc.contributor.authorHeimrich, Bernden
dc.contributor.authorGasser, Thomasen
dc.contributor.authorWhitworth, Alexen
dc.contributor.authorDeleidi, Michelaen
dc.date.accessioned2018-09-08T06:30:33Z
dc.date.available2018-09-08T06:30:33Z
dc.date.issued2018-06en
dc.identifier.issn2211-1247
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/279792
dc.description.abstractWhile mitochondrial dysfunction is emerging as key in Parkinson's disease (PD), a central question remains whether mitochondria are actual disease drivers and whether boosting mitochondrial biogenesis and function ameliorates pathology. We address these questions using patient-derived induced pluripotent stem cells and Drosophila models of GBA-related PD (GBA-PD), the most common PD genetic risk. Patient neurons display stress responses, mitochondrial demise, and changes in NAD+ metabolism. NAD+ precursors have been proposed to ameliorate age-related metabolic decline and disease. We report that increasing NAD+ via the NAD+ precursor nicotinamide riboside (NR) significantly ameliorates mitochondrial function in patient neurons. Human neurons require nicotinamide phosphoribosyltransferase (NAMPT) to maintain the NAD+ pool and utilize NRK1 to synthesize NAD+ from NAD+ precursors. Remarkably, NR prevents the age-related dopaminergic neuronal loss and motor decline in fly models of GBA-PD. Our findings suggest NR as a viable clinical avenue for neuroprotection in PD and other neurodegenerative diseases. Mitochondrial damage is a key feature in Parkinson's disease. Schöndorf et al. demonstrate that nicotinamide riboside, an NAD+ precursor, boosts mitochondrial function in neurons derived from Parkinson's disease patient stem cells and is neuroprotective in Parkinson's disease fly models. These findings support use of NAD+ precursors in Parkinson's and other neurodegenerative diseases.
dc.format.mediumPrinten
dc.languageengen
dc.publisherElsevier
dc.rightsAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectNeuronsen
dc.subjectMitochondriaen
dc.subjectAnimalsen
dc.subjectHumansen
dc.subjectDrosophila melanogasteren
dc.subjectParkinson Diseaseen
dc.subjectDisease Models, Animalen
dc.subjectNiacinamideen
dc.subjectNADen
dc.subjectGlucosylceramidaseen
dc.subjectMotor Activityen
dc.subjectAutophagyen
dc.subjectUnfolded Protein Responseen
dc.subjectInduced Pluripotent Stem Cellsen
dc.subjectEndoplasmic Reticulum Stressen
dc.subjectDopaminergic Neuronsen
dc.subjectMitochondrial Dynamicsen
dc.titleThe NAD+ Precursor Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in iPSC and Fly Models of Parkinson's Disease.en
dc.typeArticle
prism.endingPage2988
prism.issueIdentifier10en
prism.publicationDate2018en
prism.publicationNameCell reportsen
prism.startingPage2976
prism.volume23en
dc.identifier.doi10.17863/CAM.27162
dcterms.dateAccepted2018-05-02en
rioxxterms.versionofrecord10.1016/j.celrep.2018.05.009en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-06en
dc.contributor.orcidSanchez-Martinez, Alvaro [0000-0002-2728-6251]
dc.contributor.orcidPanagiotakopoulou, Vasiliki [0000-0002-8006-552X]
dc.contributor.orcidPruszak, Jan [0000-0003-4297-4009]
dc.contributor.orcidWhitworth, Alex [0000-0002-1154-6629]
dc.contributor.orcidDeleidi, Michela [0000-0003-0357-0124]
dc.identifier.eissn2211-1247
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UP_1501/1)
pubs.funder-project-idMRC (MC_UU_00015/6)
pubs.funder-project-idEuropean Commission FP7 ERC Starting Independent Researcher Grant (SIRG) (309742)


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