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dc.contributor.authorWalter, Jonasen_US
dc.contributor.authorBolognin, Silviaen_US
dc.contributor.authorAntony, Paul M.A.en_US
dc.contributor.authorNickels, Sarah L.en_US
dc.contributor.authorPoovathingal, Suresh K.en_US
dc.contributor.authorSalamanca, Luisen_US
dc.contributor.authorMagni, Stefanoen_US
dc.contributor.authorPerfeito, Ritaen_US
dc.contributor.authorHoel, Fredriken_US
dc.contributor.authorQing, Xiaobinen_US
dc.contributor.authorJarazo, Javieren_US
dc.contributor.authorArias-Fuenzalida, Jonathanen_US
dc.contributor.authorIgnac, Tomaszen_US
dc.contributor.authorMonzel, Anna S.en_US
dc.contributor.authorGonzalez-Cano, Lauraen_US
dc.contributor.authorPereira de Almeida, Luisen_US
dc.contributor.authorSkupin, Alexanderen_US
dc.contributor.authorTronstad, Karl Johanen_US
dc.contributor.authorSchwamborn, Jens C.en_US
dc.date.accessioned2020-06-15T16:21:20Z
dc.date.available2020-06-15T16:21:20Z
dc.date.issued2019-04-11
dc.PublishedWalter, Bolognin, Antony, Nickels, Poovathingal, Salamanca, Magni, Perfeito, Hoel, Qing, Jarazo, Arias-Fuenzalida, Ignac, Monzel, Gonzalez-Cano, Pereira de Almeida, Skupin, Tronstad, Schwamborn. Neural Stem Cells of Parkinson's Disease Patients Exhibit Aberrant Mitochondrial Morphology and Functionality.. Stem Cell Reports. 2019:12:5:878-889eng
dc.identifier.issn2213-6711
dc.identifier.urihttps://hdl.handle.net/1956/22602
dc.description.abstractSummary Emerging evidence suggests that Parkinson's disease (PD), besides being an age-associated disorder, might also have a neurodevelopment component. Disruption of mitochondrial homeostasis has been highlighted as a crucial cofactor in its etiology. Here, we show that PD patient-specific human neuroepithelial stem cells (NESCs), carrying the LRRK2-G2019S mutation, recapitulate key mitochondrial defects previously described only in differentiated dopaminergic neurons. By combining high-content imaging approaches, 3D image analysis, and functional mitochondrial readouts we show that LRRK2-G2019S mutation causes aberrations in mitochondrial morphology and functionality compared with isogenic controls. LRRK2-G2019S NESCs display an increased number of mitochondria compared with isogenic control lines. However, these mitochondria are more fragmented and exhibit decreased membrane potential. Functional alterations in LRRK2-G2019S cultures are also accompanied by a reduced mitophagic clearance via lysosomes. These findings support the hypothesis that preceding mitochondrial developmental defects contribute to the manifestation of the PD pathology later in life.en_US
dc.language.isoengeng
dc.publisherElseviereng
dc.rightsAttribution-NonCommercial-NoDerivs CC BY-NC-NDeng
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0eng
dc.titleNeural Stem Cells of Parkinson's Disease Patients Exhibit Aberrant Mitochondrial Morphology and Functionality.en_US
dc.typePeer reviewed
dc.typeJournal article
dc.date.updated2019-11-15T15:08:48Z
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2019 The Author(s)
dc.identifier.doihttps://doi.org/10.1016/j.stemcr.2019.03.004
dc.identifier.cristin1725480
dc.source.journalStem Cell Reports


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