Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/190166
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Torres, Pascual | - |
dc.contributor.author | Anerillas, Carlos | - |
dc.contributor.author | Ramírez Núñez, Omar | - |
dc.contributor.author | Fernàndez, Anna | - |
dc.contributor.author | Encinas, Mario | - |
dc.contributor.author | Povedano, Mònica | - |
dc.contributor.author | Andrés Benito, Pol | - |
dc.contributor.author | Ferrer, Isidro (Ferrer Abizanda) | - |
dc.contributor.author | Ayala, Victòria | - |
dc.contributor.author | Pamplona, Reinald | - |
dc.contributor.author | Portero Otín, Manuel | - |
dc.date.accessioned | 2022-10-25T13:59:59Z | - |
dc.date.available | 2022-10-25T13:59:59Z | - |
dc.date.issued | 2022-08-01 | - |
dc.identifier.issn | 1754-8411 | - |
dc.identifier.uri | http://hdl.handle.net/2445/190166 | - |
dc.description.abstract | To evaluate senescence mechanisms, including senescence-associated secretory phenotype (SASP), in the motor neuron disease model hSOD1-G93A, we quantified the expression of p16 and p21 and senescence-associated Ji-galactosidase (SA-Ji-gal) in nervous tissue. As SASP markers, we measured the mRNA levels of Il1a , Il6 , Ifna and Ifnb. Furthermore, we explored whether an alteration of alternative splicing is associated with senescence by measuring the Adipor2 cryptic exon inclusion levels, a specific splicing variant repressed by TAR DNA-binding protein (TDP-43; encoded by Tardbp). Transgenic mice showed an atypical senescence profile with high p16 and p21 mRNA and protein in glia, without the canonical increase in SA-Ji-gal activity. Consistent with SASP, there was an increase in Il1a and Il6 expression, associated with increased TNF-R and M-CSF protein levels, with females being partially protected. TDP-43 splicing activity was compromised in this model, and the senolytic drug Navitoclax did not alter the disease progression. This lack of effect was reproduced in vitro , in contrast to dasatinib and quercetin, which diminished p16 and p21. Our findings show a non-canonical profile of senescence biomarkers in the model hSOD1-G93A. | - |
dc.format.extent | 11 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | The Company of Biologists | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1242/dmm.049059 | - |
dc.relation.ispartof | Disease Models & Mechanisms, 2022, vol. 15, núm. 8 | - |
dc.relation.uri | https://doi.org/10.1242/dmm.049059 | - |
dc.rights | cc by (c) Torres, Pascual et al., 2022 | - |
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 | Esclerosi lateral amiotròfica | - |
dc.subject.classification | RNA | - |
dc.subject.other | Amyotrophic lateral sclerosis | - |
dc.subject.other | RNA | - |
dc.title | A motor neuron disease mouse model reveals a non-canonical profile of senescence biomarkers | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.date.updated | 2022-10-20T08:48:08Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 35916061 | - |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
dmm049059.pdf | 5.5 MB | Adobe PDF | View/Open |
This item is licensed under a
Creative Commons License