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dc.contributor.authorSchöndorf, David C
dc.contributor.authorIvanyuk, Dina
dc.contributor.authorBaden, Pascale
dc.contributor.authorSanchez-Martinez, Alvaro
dc.contributor.authorDe Cicco, Silvia
dc.contributor.authorYu, Cong
dc.contributor.authorGiunta, Ivana
dc.contributor.authorSchwarz, Lukas K
dc.contributor.authorDi Napoli, Gabriele
dc.contributor.authorPanagiotakopoulou, Vasiliki
dc.contributor.authorNestel, Sigrun
dc.contributor.authorKeatinge, Marcus
dc.contributor.authorPruszak, Jan
dc.contributor.authorBandmann, Oliver
dc.contributor.authorHeimrich, Bernd
dc.contributor.authorGasser, Thomas
dc.contributor.authorWhitworth, Alexander J
dc.contributor.authorDeleidi, Michela
dc.date.accessioned2018-09-08T06:30:33Z
dc.date.available2018-09-08T06:30:33Z
dc.date.issued2018-06-05
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.
dc.format.mediumPrint
dc.languageeng
dc.publisherElsevier BV
dc.rightsAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectNeurons
dc.subjectMitochondria
dc.subjectAnimals
dc.subjectHumans
dc.subjectDrosophila melanogaster
dc.subjectParkinson Disease
dc.subjectDisease Models, Animal
dc.subjectNiacinamide
dc.subjectNAD
dc.subjectGlucosylceramidase
dc.subjectMotor Activity
dc.subjectAutophagy
dc.subjectUnfolded Protein Response
dc.subjectInduced Pluripotent Stem Cells
dc.subjectEndoplasmic Reticulum Stress
dc.subjectDopaminergic Neurons
dc.subjectMitochondrial Dynamics
dc.titleThe NAD+ Precursor Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in iPSC and Fly Models of Parkinson's Disease.
dc.typeArticle
prism.endingPage2988
prism.issueIdentifier10
prism.publicationDate2018
prism.publicationNameCell Rep
prism.startingPage2976
prism.volume23
dc.identifier.doi10.17863/CAM.27162
dcterms.dateAccepted2018-05-02
rioxxterms.versionofrecord10.1016/j.celrep.2018.05.009
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-06
dc.contributor.orcidWhitworth, Alex [0000-0002-1154-6629]
dc.identifier.eissn2211-1247
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MC_UP_1501/1)
pubs.funder-project-idMedical Research Council (MC_UU_00015/6)
pubs.funder-project-idEuropean Research Council (309742)
cam.issuedOnline2018-06-08


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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)