ArticleAging cell2016
Lysosomal storage and impaired autophagy lead to inflammasome activation in Gaucher macrophages.
Article in Aging cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 2 of them syntheses that pooled it.
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Who cites it
90 citing papers in PubMed, 2 syntheses or guidelines pooled it, 148 citations in OpenAlex.
- Trends in Glucocerebrosides Research: A Systematic Review.Frontiers in physiology · 2020Pooled it
- Fabry disease cardiomyopathy: A state-of-the-art review.Progress in cardiovascular diseasesPooled it
- Meta-inflammation through the lens of macrophage programming and nutrient-sensing ghrelin signaling.Immunometabolism (Cobham, Surrey) · 2026Review
- Gaucher disease: the hematologist's perspective of a multisystemic disorder.Annals of hematology · 2026Review
- Transcriptomic Profiling of Monozygotic Twins with Type 1 Gaucher Disease.Life (Basel, Switzerland) · 2026Article
- Peripheral immunochemical considerations in Parkinson disease: sources, targets and crosstalk mechanisms.Journal of translational medicine · 2026Review
- Inflammasome adaptor ASC promotes sustained neuroinflammation and mild cognitive impairment in a closed-head injury model.The Journal of clinical investigation · 2026Article
- The dual impact of GBA1 in disease: from germline mutations in neurological disorders to alterations in cancer.Cell death discovery · 2026Review
- Immune cell metabolic dysfunction in Parkinson's disease.Molecular neurodegeneration · 2025Review
- Natural history of inflammation and impaired autophagy in children with Gaucher disease identified by newborn screening.Molecular genetics and metabolism reports · 2025Article
- The spectrum of lysosomal stress and damage responses: from mechanosensing to inflammation.EMBO reports · 2025Review
- Deciphering metabolic shifts in Gaucher disease type 1: a multi-omics study.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Current opinion on pluripotent stem cell technology in Gaucher's disease: challenges and future prospects.Cytotechnology · 2025Review
- Article
- Review
- Old disease-New reflections: Gaucher, immunity, and inflammation.Journal of cellular and molecular medicine · 2024Review
- Clinical, mechanistic, biomarker, and therapeutic advances in GBA1-associated Parkinson's disease.Translational neurodegeneration · 2024Review
- Unraveling the impact of lysosomal dysfunction on myeloproliferative neoplasm.Cancer medicine · 2024Article
- Systemic immune challenge exacerbates neurodegeneration in a model of neurological lysosomal disease.EMBO molecular medicine · 2024Article
- PIKfyve controls dendritic cell function and tumor immunity.bioRxiv : the preprint server for biology · 2024Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase, is characterized by the presence of glucosylcer-amide macrophages, the accumulation of glucosylceramide in lysosomes and the secretion of inflammatory cytokines. However, the connection between this lysosomal storage and inflammation is not clear. Studying macrophages derived from peripheral monocytes from patients with type 1 Gaucher disease with genotype N370S/N370S, we confirmed an increased secretion of interleukins IL-1β and IL-6. In addition, we found that activation of the inflammasome, a multiprotein complex that activates caspase-1, led to the maturation of IL-1β in Gaucher macrophages. We show that inflammasome activation in these cells is the result of impaired autophagy. Treatment with the small-molecule glucocerebrosidase chaperone NCGC758 reversed these defects, inducing autophagy and reducing IL-1β secretion, confirming the role of the deficiency of lysosomal glucocerebrosidase in these processes. We found that in Gaucher macrophages elevated levels of the autophagic adaptor p62 prevented the delivery of inflammasomes to autophagosomes. This increase in p62 led to activation of p65-NF-kB in the nucleus, promoting the expression of inflammatory cytokines and the secretion of IL-1β. This newly elucidated mechanism ties lysosomal dysfunction to inflammasome activation, and may contribute to the massive organomegaly, bone involvement and increased susceptibility to certain malignancies seen in Gaucher disease. Moreover, this link between lysosomal storage, impaired autophagy, and inflammation may have implications relevant to both Parkinson disease and the aging process. Defects in these basic cellular processes may also provide new therapeutic targets.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.