ArticleCell reports2021
Proteopathic tau primes and activates interleukin-1β via myeloid-cell-specific MyD88- and NLRP3-ASC-inflammasome pathway.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 82 citations in OpenAlex.
- Fyn kinase: a key mechanistic regulator and therapeutic target in tauopathy and neurodegenerative diseases.Translational neurodegeneration · 2026Review
- VlPAG/DRN Microglia Drive Neuropathic Pain-Induced Depression via a Defined Neuroimmune Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- NSAID use is associated with lower dementia and Alzheimer's disease prevalence and slower cognitive decline: A retrospective longitudinal analysis of the NACC cohort.medRxiv : the preprint server for health sciences · 2026Article
- d-amino acids restrain macrophage IL-1β release through gasdermin D acetylation.Science advances · 2026Article
- Immune signaling and function in neurodegeneration.The Journal of clinical investigation · 2026Review
- Tracking tau and cellular responses in human iPSC-microglia: from uptake to seedable secretion, including in extracellular vesicles.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Extracellular Vesicles in Tauopathies: Mechanisms and Applications.International journal of molecular sciences · 2026Review
- GASDERMIN D-mediated pyroptosis as a therapeutic target in TAU-dependent frontotemporal dementia mouse model.Journal of biomedical science · 2026Article
- Tau abnormalities and microglial remodeling in glaucoma: potential links to phagocytosis-related injury.Frontiers in neurology · 2026Review
- Peripheral and central inflammation in progressive supranuclear palsy syndrome: an immunological and imaging neuroinflammation study.Frontiers in immunology · 2026Article
- The deubiquitinase OTULIN regulates tau expression and RNA metabolism in neurons.Genomic psychiatry : advancing science from genes to society · 2025Article
- Porcine GWAS identifies ACOT11 as regulator for macrophage IL-1β maturation via IFNGR2 palmitoylation.Science China. Life sciences · 2025Article
- Emerging roles for innate and adaptive immunity in tauopathies.Cell reports · 2025Review
- The Potential for Extracellular Vesicles in Nanomedicine: A Review of Recent Advancements and Challenges Ahead.Advanced biology · 2025Review
- The Therapeutic Potential of Butyrate and Lauric Acid in Modulating Glial and Neuronal Activity in Alzheimer's Disease.Nutrients · 2025Review
- Research Progress in the Molecular Mechanism of NLRP3 Inflammasome in Alzheimer's Disease and Regulation by Natural Plant Products.Molecular neurobiology · 2025Review
- The Inflammasome-miR Axis in Alzheimer's Disease and Chronic Pain: Molecular Mechanisms and Therapeutic Opportunities.Aging and disease · 2025Review
- pS396/pS404 (PHF1) tau vaccine outperforms pS199/pS202 (AT8) in rTg4510 tauopathy model.NPJ vaccines · 2025Article
- TLR2 promotes the progression of diabetes mellitus with atherosclerosis via activating NLRP3 inflammasome and MyD88/NF-κB signaling pathway.Scientific reports · 2025Article
- Alzheimer's disease as an auto-innate immune pathology with potential cell trans-differentiation and enhanced trained immunity in 3xTg-AD mouse model.Journal of Alzheimer's disease : JAD · 2025Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
Abstract
Pathological hyperphosphorylation and aggregation of tau (pTau) and neuroinflammation, driven by interleukin-1β (IL-1β), are the major hallmarks of tauopathies. Here, we show that pTau primes and activates IL-1β. First, RNA-sequence analysis suggests paired-helical filaments (PHFs) from human tauopathy brain primes nuclear factor κB (NF-κB), chemokine, and IL-1β signaling clusters in human primary microglia. Treating microglia with pTau-containing neuronal media, exosomes, or PHFs causes IL-1β activation, which is NLRP3, ASC, and caspase-1 dependent. Suppression of pTau or ASC reduces tau pathology and inflammasome activation in rTg4510 and hTau mice, respectively. Although the deletion of MyD88 prevents both IL-1β expression and activation in the hTau mouse model of tauopathy, ASC deficiency in myeloid cells reduces pTau-induced IL-1β activation and improves cognitive function in hTau mice. Finally, pTau burden co-exists with elevated IL-1β and ASC in autopsy brains of human tauopathies. Together, our results suggest pTau activates IL-1β via MyD88- and NLRP3-ASC-dependent pathways in myeloid cells, including microglia.
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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.