Defective mitochondrial DNA homeostasis in the substantia nigra in Parkinson disease

dc.contributor.author Dölle, Christian dc.contributor.author Flønes, Irene Hana dc.contributor.author Sanchez Nido, Gonzalo dc.contributor.author Miletic, Hrvoje dc.contributor.author Osuagwu, Nelson dc.contributor.author Kristoffersen, Stine dc.contributor.author Lilleng, Peer Kåre dc.contributor.author Larsen, Jan Petter dc.contributor.author Tysnes, Ole-Bjørn dc.contributor.author Haugarvoll, Kristoffer dc.contributor.author Bindoff, Laurence dc.contributor.author Tzoulis, Charalampos dc.date.accessioned 2017-05-18T07:49:32Z dc.date.available 2017-05-18T07:49:32Z dc.date.created 2016-12-18T15:13:21Z dc.date.issued 2016-11 dc.identifier.citation Dölle, C. et al (2016) Defective mitochondrial DNA homeostasis in the substantia nigra in Parkinson disease. Nature Communications. 2016, 7:13548 . nb_NO dc.identifier.issn 2041-1723 dc.identifier.uri hdl.handle.net/11250/2442708 dc.description.abstract Increased somatic mitochondrial DNA (mtDNA) mutagenesis causes premature aging in mice, and mtDNA damage accumulates in the human brain with aging and neurodegenerative disorders such as Parkinson disease (PD). Here, we study the complete spectrum of mtDNA changes, including deletions, copy-number variation and point mutations, in single neurons from the dopaminergic substantia nigra and other brain areas of individuals with Parkinson disease and neurologically healthy controls. We show that in dopaminergic substantia nigra neurons of healthy individuals, mtDNA copy number increases with age, maintaining the pool of wild-type mtDNA population in spite of accumulating deletions. This upregulation fails to occur in individuals with Parkinson disease, however, resulting in depletion of the wild-type
mtDNA population. By contrast, neuronal mtDNA point mutational load is not increased in Parkinson disease. Our findings suggest that dysregulation of mtDNA homeostasis is a key process in the pathogenesis of neuronal loss in Parkinson disease. nb_NO dc.language.iso eng nb_NO dc.rights Navngivelse 4.0 Internasjonal * dc.rights.uri creativecommons.org/licenses/by/4.0/deed.no * dc.subject mitochondrial DNA nb_NO dc.subject neurodegenerative disorders nb_NO dc.subject nevrodegenerativ sykdom nb_NO dc.subject parkinsonisme nb_NO dc.title Defective mitochondrial DNA homeostasis in the substantia nigra in Parkinson disease nb_NO dc.type Journal article nb_NO dc.type Peer reviewed nb_NO dc.description.version publishedVersion dc.rights.holder © The authors nb_NO dc.subject.nsi VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Nevrologi: 752 nb_NO dc.source.pagenumber 11 nb_NO dc.source.volume 7 nb_NO dc.source.journal Nature Communications nb_NO dc.identifier.doi 10.1038/ncomms13548 dc.identifier.cristin 1414696 cristin.unitcode 217,7,2,0 cristin.unitname Institutt for helsefag cristin.ispublished true cristin.fulltext original cristin.qualitycode 2

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