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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/190166
A motor neuron disease mouse model reveals a non-canonical profile of senescence biomarkers
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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.
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TORRES, Pascual, ANERILLAS, Carlos, RAMÍREZ NÚÑEZ, Omar, FERNÀNDEZ, Anna, ENCINAS, Mario, POVEDANO, Mònica, ANDRÉS BENITO, Pol, FERRER, Isidro (ferrer abizanda), AYALA, Victòria, PAMPLONA, Reinald, PORTERO-OTIN, Manuel. A motor neuron disease mouse model reveals a non-canonical profile of senescence biomarkers. _Disease Models & Mechanisms_. 2022. Vol. 15, núm. 8. [consulta: 23 de gener de 2026]. ISSN: 1754-8411. [Disponible a: https://hdl.handle.net/2445/190166]