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http://hdl.handle.net/2445/171935
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DC Field | Value | Language |
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dc.contributor.author | Martínez González, Loreto | - |
dc.contributor.author | Rodríguez Cueto, Carmen | - |
dc.contributor.author | Cabezudo, Diego | - |
dc.contributor.author | Bartolomé, Fernando | - |
dc.contributor.author | Andrés Benito, Pol | - |
dc.contributor.author | Ferrer, Isidro (Ferrer Abizanda) | - |
dc.contributor.author | Gil, Carmen | - |
dc.contributor.author | Martín Requero, Ángeles | - |
dc.contributor.author | Fernández Ruiz, Javier | - |
dc.contributor.author | Martínez, Ana | - |
dc.contributor.author | Lago, Eva de | - |
dc.date.accessioned | 2020-11-10T11:36:21Z | - |
dc.date.available | 2020-11-10T11:36:21Z | - |
dc.date.issued | 2020-03-10 | - |
dc.identifier.issn | 2045-2322 | - |
dc.identifier.uri | http://hdl.handle.net/2445/171935 | - |
dc.description.abstract | athogenesis of amyotrophic lateral sclerosis (ALS), a devastating disease where no treatment exists, involves the compartmentalization of the nuclear protein TDP-43 (TAR DNA-binding protein 43) in the cytoplasm which is promoted by its aberrant phosphorylation and others posttranslational modifications. Recently, it was reported that CK-1δ (protein casein kinase-1δ) is able to phosphorylate TDP-43. Here, the preclinical efficacy of a benzothiazole-based CK-1δ inhibitor IGS-2.7, both in a TDP-43 (A315T) transgenic mouse and in a human cell-based model of ALS, is shown. Treatment with IGS-2.7 produces a significant preservation of motor neurons in the anterior horn at lumbar level, a decrease in both astroglial and microglial reactivity in this area, and in TDP-43 phosphorylation in spinal cord samples. Furthermore, the recovery of TDP-43 homeostasis (phosphorylation and localization) in a human-based cell model from ALS patients after treatment with IGS-2.7 is also reported. Moreover, we have shown a trend to increase in CK-1δ mRNA in spinal cord and significantly in frontal cortex of sALS cases. All these data show for the first time the in vivo modulation of TDP-43 toxicity by CK-1δ inhibition with IGS-2.7, which may explain the benefits in the preservation of spinal motor neurons and point to the relevance of CK-1δ inhibitors in a future disease-modifying treatment for ALS. | - |
dc.format.extent | 12 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Nature Publishing Group | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1038/s41598-020-61265-y | - |
dc.relation.ispartof | Scientific Reports, 2020, vol. 10, p. 4449 | - |
dc.relation.uri | https://doi.org/10.1038/s41598-020-61265-y | - |
dc.rights | cc-by (c) Martínez González, Loreto et al., 2020 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Patologia i Terapèutica Experimental) | - |
dc.subject.classification | Esclerosi lateral amiotròfica | - |
dc.subject.classification | Proteïnes quinases | - |
dc.subject.other | Amyotrophic lateral sclerosis | - |
dc.subject.other | Protein kinases | - |
dc.title | Motor neuron preservation and decrease of in vivo TDP-43 phosphorylation by protein CK-1δ kinase inhibitor treatment | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 701934 | - |
dc.date.updated | 2020-11-10T11:36:21Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 32157143 | - |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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File | Description | Size | Format | |
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701934.pdf | 3.66 MB | Adobe PDF | View/Open |
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