dc.contributor.author | Walter, Jonas | en_US |
dc.contributor.author | Bolognin, Silvia | en_US |
dc.contributor.author | Antony, Paul M.A. | en_US |
dc.contributor.author | Nickels, Sarah L. | en_US |
dc.contributor.author | Poovathingal, Suresh K. | en_US |
dc.contributor.author | Salamanca, Luis | en_US |
dc.contributor.author | Magni, Stefano | en_US |
dc.contributor.author | Perfeito, Rita | en_US |
dc.contributor.author | Hoel, Fredrik | en_US |
dc.contributor.author | Qing, Xiaobin | en_US |
dc.contributor.author | Jarazo, Javier | en_US |
dc.contributor.author | Arias-Fuenzalida, Jonathan | en_US |
dc.contributor.author | Ignac, Tomasz | en_US |
dc.contributor.author | Monzel, Anna S. | en_US |
dc.contributor.author | Gonzalez-Cano, Laura | en_US |
dc.contributor.author | Pereira de Almeida, Luis | en_US |
dc.contributor.author | Skupin, Alexander | en_US |
dc.contributor.author | Tronstad, Karl Johan | en_US |
dc.contributor.author | Schwamborn, Jens C. | en_US |
dc.date.accessioned | 2020-06-15T16:21:20Z | |
dc.date.available | 2020-06-15T16:21:20Z | |
dc.date.issued | 2019-04-11 | |
dc.Published | Walter, 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. 2019:12:5:878-889 | eng |
dc.identifier.issn | 2213-6711 | |
dc.identifier.uri | https://hdl.handle.net/1956/22602 | |
dc.description.abstract | Summary 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.iso | eng | eng |
dc.publisher | Elsevier | eng |
dc.rights | Attribution-NonCommercial-NoDerivs CC BY-NC-ND | eng |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | eng |
dc.title | Neural Stem Cells of Parkinson's Disease Patients Exhibit Aberrant Mitochondrial Morphology and Functionality. | en_US |
dc.type | Peer reviewed | |
dc.type | Journal article | |
dc.date.updated | 2019-11-15T15:08:48Z | |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2019 The Author(s) | |
dc.identifier.doi | https://doi.org/10.1016/j.stemcr.2019.03.004 | |
dc.identifier.cristin | 1725480 | |
dc.source.journal | Stem Cell Reports | |