NLRP3 inflammasome inhibition rescues Hutchinson-Gilford Progeria cellular phenotype and extend longevity of an animal model
Alcocer-Gomez, E.; Castejon-Vega, B.; Nunez-Vasco, J.; Lendines-Cordero, D.; Navarro-Pando, J. M.; Cordero, M. D.
Show abstract
Inflammation is a hallmark of aging and accelerated aging syndromes. In this context, inflammation has been associated to the pathophysiology of Hutchinson-Gilford progeria syndrome (HGPS). In this study, we report that progeroid skin fibroblasts and animal models present an hyperactivation of the NLRP3-inflammasome complex. High expression of NLRP3 and caspase 1 was also observed in skin fibroblasts from HGPS associated to the nuclei morphology. Lymphoblast from HGPS also showed increased basal levels of NLRP3 and caspase 1 independent to the induction from metabolic factors. Consistent with these results, Zmpste24-/- showed high expression of Nlrp3 and caspase 1 in heart, liver and kidney and reduced levels of Nlrc3, however these changes were not observed in other inflammasomes. We also show that pharmacological inhibition of NLRP3 using a direct NLRP3 inhibitor, MCC950, improved cellular phenotype, significantly extends the lifespan of these progeroid animals and reduced inflammasome-dependent inflammation. These findings suggest the NLRP3-inflammasome comples as a therapeutic approach for patients with HGPS.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Epidermal stem cell compartment remains unaffected through aging in naked mole-rats. 94%
- Crosstalk between age accumulated DNA-damage and the SIRT1-AKT-GSK3b axis in urine derived renal progenitor cells 94%
- Hippocampal Transcriptome Profiling Reveals Common Disease Pathways in Chronic Hypoperfusion and Ageing 94%
Similar papers in this journal
- Similar metabolic pathways are affected in both Congenital Myasthenic Syndrome 22 and Prader Willi Syndrome 93%
- SMDT1 variants impair EMRE-mediated mitochondrial calcium uptake in patients with muscle involvement 91%
- Optineurin deficiency induces patchy hair loss but it is not sufficient to cause amyotrophic lateral sclerosis in mice 91%
Similar papers in this journal
- Investigating the Role and Regulation of GPNMB in Progranulin-deficient Macrophages 92%
- The AMD-associated genetic polymorphism CFH Y402H confers vulnerability to Hydroquinone-induced stress in iPSC-RPE cells 92%
- MiR-34a deficiency enhances nucleic acid sensing and type I IFN signaling in a mouse model of Alzheimer's disease 92%
Similar papers in this journal
- Immune modulating drug MP1032 with SARS-CoV-2 antiviral activity in vitro: A potential multi-target approach for prevention and early intervention treatment of COVID-19 92%
- Live cell imaging of single neurotrophin receptor molecules on human neuron in Alzheimer's disease 92%
- CFH loss in human RPE cells leads to inflammation and complement system dysregulation via the NF-B pathway 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.