Prion Pathogenesis in the Absence of NLRP3/ASC Inflammasomes
Open accessAbstract
The accumulation of the scrapie prion protein PrPSc, a misfolded conformer of the cellular prion protein PrPC, is a crucial feature of prion diseases. In the central nervous system, this process is accompanied by conspicuous microglia activation. The NLRP3 inflammasome is a multi-molecular complex which can sense heterogeneous pathogen-associated molecular patterns and culminates in the activation of caspase 1 and release of IL 1β. The NLRP3 inflammasome was reported to be essential for IL 1β release after in vitro exposure to the amyloidogenic peptide PrP106-126 and to recombinant PrP fibrils. We therefore studied the role of the NLRP3 inflammasome in a mouse model of prion infection. Upon intracerebral inoculation with scrapie prions (strain RML), mice lacking NLRP3 (Nlrp3-/-) or the inflammasome adaptor protein ASC (Pycard-/-) succumbed to scrapie with attack rates and incubation times similar to wild-type mice, and developed the classic histologic and biochemical features of prion diseases. Genetic ablation of NLRP3 or ASC did not significantly impact on brain levels of IL 1β at the terminal stage of disease. Our results exclude a significant role for NLRP3 and ASC in prion pathogenesis and invalidate their claimed potential as therapeutic target against prion diseases.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Knockout of NLRP3 or the adaptor protein ASC does not influence the prion disease course.
“In contrast to AD, the knockout of NLRP3 or the adaptor protein ASC does not influence the prion disease course [80].”
From Loss of Homeostatic Microglia Signature in Prion Diseases (2022) · cites this paper as [80]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 73 · Cited by 39
- Authors
- Nuvolone, M., Sorce, S., Schwarz, P., & Aguzzi, A.
- Affiliations
- University Hospital Zurich (CH)
- Corresponding author
- Nuvolone, Mario
- Aguzzi, Adriano
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-02-11
- Volume
- 10
- Issue
- 2
- Pages
- e0117208
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4324825
- OpenAlex
- W1981632978
- Cited by
- 39
- References
- 73
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 4 · 2020: 7 · 2019: 4 · 2018: 5 · 2017: 7 · 2016: 1
- FWCI
- 1.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- European Commission (222887, 278611)
- Collegio Ghislieri di Pavia
- Universität Zürich
- SystemsX.ch
- FP7 Ideas: European Research Council (250356)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- prion disease, scrapie, NLRP3 inflammasome, ASC, PYCARD, IL-1β, caspase-1, microglial activation, prion protein accumulation, NLRP3 knockout mice, prion pathogenesis, therapeutic target
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Carrier Proteins, RNA, Messenger, Prion Diseases, Apoptosis Regulatory Proteins, Mice, CARD Signaling Adaptor Proteins, Inflammasomes
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
