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dc.contributor.author | Sánchez-Danés, Adriana |
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dc.contributor.author | Richaud-Patin, Yvonne |
dc.contributor.author | Carballo Carbajal, Iria |
dc.contributor.author | Jiménez-Delgado, Senda |
dc.contributor.author | Caig, Carles |
dc.contributor.author | Mora, Sergio |
dc.contributor.author | Di Guglielmo, Claudia |
dc.contributor.author | Ezquerra, Mario |
dc.contributor.author | Patel, Bindiben |
dc.contributor.author | Giralt Torroella, Albert |
dc.contributor.author | Canals i Coll, Josep M. |
dc.contributor.author | Memo, Maurizio |
dc.contributor.author | Alberch i Vié, Jordi |
dc.contributor.author | López-Barneo, José |
dc.contributor.author | Vila Farré, Miquel |
dc.contributor.author | Cuervo, Ana Maria |
dc.contributor.author | Tolosa, Eduardo |
dc.contributor.author | Consiglio, Antonella |
dc.contributor.author | Raya Chamorro, Ángel |
dc.date | 2019-05-24T16:19:00Z |
dc.date | 2019-05-24T16:19:00Z |
dc.date | 2012-05 |
dc.date | 2019-05-24T16:19:00Z |
dc.identifier | 1757-4676 |
dc.identifier | 615356 |
dc.identifier | 22407749 |
dc.identifier.uri | http://hdl.handle.net/2445/133843 |
dc.description | Induced pluripotent stem cells (iPSC) offer an unprecedented opportunity to model human disease in relevant cell types, but it is unclear whether they could successfully model age-related diseases such as Parkinson's disease (PD). Here, we generated iPSC lines from seven patients with idiopathic PD (ID-PD), four patients with familial PD associated to the G2019S mutation in the Leucine-Rich Repeat Kinase 2 (LRRK2) gene (LRRK2-PD) and four age- and sex-matched healthy individuals (Ctrl). Over long-time culture, dopaminergic neurons (DAn) differentiated from either ID-PD- or LRRK2-PD-iPSC showed morphological alterations, including reduced numbers of neurites and neurite arborization, as well as accumulation of autophagic vacuoles, which were not evident in DAn differentiated from Ctrl-iPSC. Further induction of autophagy and/or inhibition of lysosomal proteolysis greatly exacerbated the DAn morphological alterations, indicating autophagic compromise in DAn from ID-PD- and LRRK2-PD-iPSC, which we demonstrate occurs at the level of autophagosome clearance. Our study provides an iPSC-based in vitro model that captures the patients' genetic complexity and allows investigation of the pathogenesis of both sporadic and familial PD cases in a disease-relevant cell type. |
dc.format | 16 p. |
dc.format | application/pdf |
dc.language | eng |
dc.publisher | EMBO Press |
dc.relation | Reproducció del document publicat a: https://doi.org/10.1002/emmm.201200215 |
dc.relation | EMBO Molecular Medicine, 2012, vol. 4, num. 5, p. 380-395 |
dc.relation | https://doi.org/10.1002/emmm.201200215 |
dc.rights | (c) EMBO, 2012 |
dc.rights | info:eu-repo/semantics/openAccess |
dc.subject | Dopamina |
dc.subject | Metabolisme |
dc.subject | Fenotip |
dc.subject | Genètica |
dc.subject | Neurones |
dc.subject | Malaltia de Parkinson |
dc.subject | Patologia |
dc.subject | Cèl·lules mare |
dc.subject | Dopamine |
dc.subject | Metabolism |
dc.subject | Phenotype |
dc.subject | Genetics |
dc.subject | Neurons |
dc.subject | Parkinson's disease |
dc.subject | Pathology |
dc.subject | Stem cells |
dc.title | Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson's disease |
dc.type | info:eu-repo/semantics/article |
dc.type | info:eu-repo/semantics/publishedVersion |