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http://hdl.handle.net/2445/141851
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DC Field | Value | Language |
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dc.contributor.author | Domenico, Angelique Di | - |
dc.contributor.author | Carola, Giulia | - |
dc.contributor.author | Calatayud Aristoy, Carles | - |
dc.contributor.author | Pons-Espinal, Meritxell | - |
dc.contributor.author | Muñoz, Juan Pablo | - |
dc.contributor.author | Richaud-Patin, Yvonne | - |
dc.contributor.author | Fernandez-Carasa, Irene | - |
dc.contributor.author | Gut, Marta | - |
dc.contributor.author | Faella, Armida | - |
dc.contributor.author | Parameswaran, Janani | - |
dc.contributor.author | Soriano i Fradera, Jordi | - |
dc.contributor.author | Ferrer, Isidro (Ferrer Abizanda) | - |
dc.contributor.author | Tolosa, Eduardo | - |
dc.contributor.author | Zorzano Olarte, Antonio | - |
dc.contributor.author | Cuervo, Ana Maria | - |
dc.contributor.author | Raya Chamorro, Ángel | - |
dc.contributor.author | Consiglio, Antonella | - |
dc.date.accessioned | 2019-10-08T15:40:01Z | - |
dc.date.available | 2019-10-08T15:40:01Z | - |
dc.date.issued | 2019-02-12 | - |
dc.identifier.issn | 2213-6711 | - |
dc.identifier.uri | http://hdl.handle.net/2445/141851 | - |
dc.description.abstract | Parkinson's disease (PD) is associated with the degeneration of ventral midbrain dopaminergic neurons (vmDAns) and the accumulation of toxic α-synuclein. A non-cell-autonomous contribution, in particular of astrocytes, during PD pathogenesis has been suggested by observational studies, but remains to be experimentally tested. Here, we generated induced pluripotent stem cell-derived astrocytes and neurons from familial mutant LRRK2 G2019S PD patients and healthy individuals. Upon co-culture on top of PD astrocytes, control vmDAns displayed morphological signs of neurodegeneration and abnormal, astrocyte-derived α-synuclein accumulation. Conversely, control astrocytes partially prevented the appearance of disease-related phenotypes in PD vmDAns. We additionally identified dysfunctional chaperone-mediated autophagy (CMA), impaired macroautophagy, and progressive α-synuclein accumulation in PD astrocytes. Finally, chemical enhancement of CMA protected PD astrocytes and vmDAns via the clearance of α-synuclein accumulation. Our findings unveil a crucial non-cell-autonomous contribution of astrocytes during PD pathogenesis, and open the path to exploring novel therapeutic strategies aimed at blocking the pathogenic cross talk between neurons and glial cells. | - |
dc.format.extent | 17 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Elsevier | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1016/j.stemcr.2018.12.011 | - |
dc.relation.ispartof | Stem Cell Reports, 2019, vol. 12, num. 2, p. 213-229 | - |
dc.relation.uri | https://doi.org/10.1016/j.stemcr.2018.12.011 | - |
dc.rights | cc-by (c) Domenico, Angelique Di et al., 2019 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Patologia i Terapèutica Experimental) | - |
dc.subject.classification | Malaltia de Parkinson | - |
dc.subject.classification | Astròcits | - |
dc.subject.classification | Autofàgia | - |
dc.subject.classification | Alfa-sinucleïna | - |
dc.subject.other | Parkinson's disease | - |
dc.subject.other | Astrocytes | - |
dc.subject.other | Autophagy | - |
dc.subject.other | Alpha-synuclein | - |
dc.title | Patient-specific iPSC-derived astrocytes contribute to non-cell-autonomous neurodegeneration in Parkinson's disease | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 687541 | - |
dc.date.updated | 2019-10-08T15:40:01Z | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/311736/EU//PD-HUMMODEL | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 30639209 | - |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona)) Articles publicats en revistes (Patologia i Terapèutica Experimental) Publicacions de projectes de recerca finançats per la UE Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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687541.pdf | 8.04 MB | Adobe PDF | View/Open |
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