ER Lipid Defects in Neuropeptidergic Neurons Impair Sleep Patterns in Parkinson's Disease
DC Element | Wert | Sprache |
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dc.contributor.author | Valadas, Jorge S. | |
dc.contributor.author | Esposito, Giovanni | |
dc.contributor.author | Vandekerkhove, Dirk | |
dc.contributor.author | Miskiewicz, Katarzyna | |
dc.contributor.author | Deaulmerie, Liesbeth | |
dc.contributor.author | Raitano, Susanna | |
dc.contributor.author | Seibler, Philip | |
dc.contributor.author | Klein, Christine | |
dc.contributor.author | Verstreken, Patrik | |
dc.date.accessioned | 2021-12-23T16:19:08Z | - |
dc.date.available | 2021-12-23T16:19:08Z | - |
dc.date.issued | 2018 | |
dc.identifier.issn | 08966273 | |
dc.identifier.uri | https://osnascholar.ub.uni-osnabrueck.de/handle/unios/13004 | - |
dc.description.abstract | Parkinson's disease patients report disturbed sleep patterns long before motor dysfunction. Here, in parkin and pink1 models, we identify circadian rhythm and sleep pattern defects and map these to specific neuropeptidergic neurons in fly models and in hypothalamic neurons differentiated from patient induced pluripotent stem cells (iPSCs). Parkin and Pink1 control the clearance of mitochondria by protein ubiquitination. Although we do not observe major defects in mitochondria of mutant neuropeptidergic neurons, we do find an excess of endoplasmic reticulum-mitochondrial contacts. These excessive contact sites cause abnormal lipid trafficking that depletes phosphatidylserine from the endoplasmic reticulum (ER) and disrupts the production of neuropeptide-containing vesicles. Feeding mutant animals phosphatidylserine rescues neuropeptidergic vesicle production and acutely restores normal sleep patterns in mutant animals. Hence, sleep patterns and circadian disturbances in Parkinson's disease models are explained by excessive ER-mitochondrial contacts, and blocking their formation or increasing phosphatidylserine levels rescues the defects in vivo. | |
dc.description.sponsorship | ERCEuropean Research Council (ERC)European Commission [646671]; FWO VlaanderenFWO; Hercules Foundation; IWTInstitute for the Promotion of Innovation by Science and Technology in Flanders (IWT); BELSPO-IAPBelgian Federal Science Policy Office; Methusalem grant of the Flemish government; Opening the Future; Vlaamse Parkinsonliga; VIB; Fundacao para a Ciencia e a Tecnologia (FCT)Portuguese Foundation for Science and TechnologyEuropean Commission [SFRH/BD/88363/2012]; We thank the Bloomington, Harvard, and Kyoto Drosophila stock centers and the Developmental Studies Hybridoma bank as well as Bart De Strooper, Patrick Callaerts, Sha Liu, Edwin S. Levitan, Wim Vandenberghe, and Rose Goodchild for reagents. We thank Bart De Strooper, Sha Liu, Wim Vandenberghe, Georg Halder, Vanessa A. Morais, Rose Goodchild, Joseph McInnes, Sabine Kuenen, Antonio Laranjeira, Elsa Lauwers, Ana Rita Santos, the VIB BioImaging core facility, and all members of the Verstreken lab for discussions and help. This work was supported by an ERC Consolidator Grant (646671), the FWO Vlaanderen, the Hercules Foundation, IWT, BELSPO-IAP, a Methusalem grant of the Flemish government, Opening the Future, the Vlaamse Parkinsonliga, and VIB. J.S.V. is supported by the Fundacao para a Ciencia e a Tecnologia (FCT, grant number SFRH/BD/88363/2012), D.V. is supported by the FWO Vlaanderen, and P.V. is a member of the FENS Kavli Network of Excellence. | |
dc.language.iso | en | |
dc.publisher | CELL PRESS | |
dc.relation.ispartof | NEURON | |
dc.subject | ANIMAL-MODELS | |
dc.subject | CIRCADIAN-RHYTHMS | |
dc.subject | DROSOPHILA-MELANOGASTER | |
dc.subject | ENDOPLASMIC-RETICULUM | |
dc.subject | INCREASED SENSITIVITY | |
dc.subject | MITOCHONDRIA-ASSOCIATED MEMBRANES | |
dc.subject | MOUSE-BRAIN | |
dc.subject | Neurosciences | |
dc.subject | Neurosciences & Neurology | |
dc.subject | NONMOTOR SYMPTOMS | |
dc.subject | PINK1-PARKIN PATHWAY | |
dc.subject | PLURIPOTENT STEM-CELLS | |
dc.title | ER Lipid Defects in Neuropeptidergic Neurons Impair Sleep Patterns in Parkinson's Disease | |
dc.type | journal article | |
dc.identifier.doi | 10.1016/j.neuron.2018.05.022 | |
dc.identifier.isi | ISI:000436587600015 | |
dc.description.volume | 98 | |
dc.description.issue | 6 | |
dc.description.startpage | 1155+ | |
dc.contributor.orcid | 0000-0002-2126-9485 | |
dc.contributor.researcherid | K-4142-2019 | |
dc.identifier.eissn | 10974199 | |
dc.publisher.place | 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA | |
dcterms.isPartOf.abbreviation | Neuron | |
dcterms.oaStatus | Bronze, Green Accepted |
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geprüft am 01.06.2024