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DC Field | Value | Language |
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dc.contributor.author | Tristá Noguero, Alba | - |
dc.contributor.author | Fernández Carasa, Irene | - |
dc.contributor.author | Calatayud, Carles | - |
dc.contributor.author | Bermejo Casadesús, Cristina | - |
dc.contributor.author | Pons Espinal, Meritxell | - |
dc.contributor.author | Colini Baldeschi, Arianna | - |
dc.contributor.author | Campa, Leticia | - |
dc.contributor.author | Artigas, Francesc | - |
dc.contributor.author | Bortolozzi, Analia | - |
dc.contributor.author | Domingo Jiménez, Rosario | - |
dc.contributor.author | Ibáñez, Salvador | - |
dc.contributor.author | Pineda, Mercè | - |
dc.contributor.author | Artuch Iriberri, Rafael | - |
dc.contributor.author | Raya, Ángel | - |
dc.contributor.author | García Cazorla, Àngels | - |
dc.contributor.author | Consiglio, Antonella | - |
dc.date.accessioned | 2023-05-23T09:59:43Z | - |
dc.date.available | 2023-05-23T09:59:43Z | - |
dc.date.issued | 2023-02-06 | - |
dc.identifier.issn | 1757-4684 | - |
dc.identifier.uri | http://hdl.handle.net/2445/198344 | - |
dc.description.abstract | Tyrosine hydroxylase deficiency (THD) is a rare genetic disorder leading to dopaminergic depletion and early-onset Parkinsonism. Affected children present with either a severe form that does not respond to L-Dopa treatment (THD-B) or a milder L-Dopa responsive form (THD-A). We generated induced pluripotent stem cells (iPSCs) from THD patients that were differentiated into dopaminergic neurons (DAn) and compared with control-DAn from healthy individuals and gene-corrected isogenic controls. Consistent with patients, THD iPSC-DAn displayed lower levels of DA metabolites and reduced TH expression, when compared to controls. Moreover, THD iPSC-DAn showed abnormal morphology, including reduced total neurite length and neurite arborization defects, which were not evident in DAn differentiated from control-iPSC. Treatment of THD-iPSC-DAn with L-Dopa rescued the neuronal defects and disease phenotype only in THDA-DAn. Interestingly, L-Dopa treatment at the stage of neuronal precursors could prevent the alterations in THDB-iPSC-DAn, thus suggesting the existence of a critical developmental window in THD. Our iPSC-based model recapitulates THD disease phenotypes and response to treatment, representing a promising tool for investigating pathogenic mechanisms, drug screening, and personalized management. | - |
dc.format.extent | 15 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | EMBO | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.15252/emmm.202215847 | - |
dc.relation.ispartof | EMBO Molecular Medicine, 2023, vol. 15, num. 3, p. e15847 | - |
dc.relation.uri | https://doi.org/10.15252/emmm.202215847 | - |
dc.rights | cc by (c) Tristá Noguero, Alba et al., 2023 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.source | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) | - |
dc.subject.classification | Malalties rares | - |
dc.subject.classification | Cèl·lules mare | - |
dc.subject.classification | Fenotip | - |
dc.subject.classification | Dopamina | - |
dc.subject.other | Rare diseases | - |
dc.subject.other | Stem cells | - |
dc.subject.other | Phenotype | - |
dc.subject.other | Dopamine | - |
dc.title | IPSC‐based modeling of THD recapitulates disease phenotypes and reveals neuronal malformation | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.date.updated | 2023-04-14T11:15:49Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 36740977 | - |
Appears in Collections: | Articles publicats en revistes (Institut de Biomedicina (IBUB)) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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File | Description | Size | Format | |
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EMBO Mol Med - 2023 - Trist n‐Noguero - iPSC‐based modeling of THD recapitulates disease phenotypes and reveals neuronal.pdf | 18.16 MB | Adobe PDF | View/Open |
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