Affinage

NLRP3

NACHT, LRR and PYD domains-containing protein 3 · UniProt Q96P20

Round 2 corrected
Length
1036 aa
Mass
118.2 kDa
Annotated
2026-04-29
130 papers in source corpus 50 papers cited in narrative 50 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NLRP3 is a cytosolic pattern recognition receptor and inflammasome scaffold that integrates diverse danger signals—including K⁺ efflux, lysosomal rupture, mitochondrial damage, crystalline particles, and lipotoxic species—into caspase-1-dependent IL-1β/IL-18 maturation and pyroptotic cell death. In its resting state, NLRP3 forms a 12–16-mer double-ring cage with shielded pyrin domains that localizes to membranes including the trans-Golgi network; activation requires a two-step process in which NF-κB-dependent transcriptional priming induces NLRP3 expression, followed by post-translational licensing—including deubiquitination by BRCC3/BRISC, palmitoylation by ZDHHC5/ZDHHC7 promoting TGN localization, and SUMOylation by TRIM28/UBC9—that enables NEK7 binding across the LRR and NACHT domains, oligomerization, PYD-mediated ASC filament nucleation, and CARD-mediated caspase-1 recruitment (PMID:34861190, PMID:31189953, PMID:24630722, PMID:26814970, PMID:38092000, PMID:38583156, PMID:23246432, PMID:34373456). Gain-of-function mutations in NLRP3 cause the cryopyrin-associated periodic syndromes (CAPS), including familial cold autoinflammatory syndrome and Muckle–Wells syndrome (PMID:11687797).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2001 High

    Identification of NLRP3 as a PYD–NACHT–LRR-containing gene whose gain-of-function mutations cause FCAS and Muckle–Wells syndrome established it as a critical regulator of autoinflammation.

    Evidence Positional cloning and direct sequencing of genomic DNA from affected families

    PMID:11687797

    Open questions at the time
    • Biochemical function of NLRP3 protein unknown
    • Downstream effectors and signaling pathway uncharacterized
  2. 2004 High

    Demonstration that NLRP3 assembles with ASC and caspase-1 into an inflammasome complex with IL-1β-processing activity resolved the molecular platform through which NLRP3 signals.

    Evidence Co-immunoprecipitation, reconstitution of inflammasome complex, patient macrophage assays

    PMID:15030775

    Open questions at the time
    • Physiological activating stimuli unknown
    • Structural basis of complex assembly not resolved
  3. 2006 High

    Discovery that urate and pyrophosphate crystals activate NLRP3 in a caspase-1/ASC-dependent manner provided the first physiological danger-signal ligands and linked NLRP3 to gout pathogenesis.

    Evidence NLRP3/ASC/caspase-1 knockout mice, in vivo peritonitis model

    PMID:16407889

    Open questions at the time
    • Mechanism of crystal sensing by NLRP3 unknown
    • Whether NLRP3 directly contacts crystals unresolved
  4. 2007 High

    Establishing that low intracellular K⁺ is both necessary and sufficient for NLRP3 activation in vitro identified K⁺ efflux as a unifying upstream signal for diverse activators.

    Evidence In vitro reconstitution at defined K⁺ concentrations, pharmacological K⁺ efflux inhibition

    PMID:17599094

    Open questions at the time
    • How K⁺ decrease is sensed by NLRP3 structurally unknown
    • Relationship between K⁺ efflux and ROS/lysosomal pathways unclear
  5. 2008 High

    Identification of lysosomal rupture/cathepsin B release (for silica and alum) and NADPH oxidase-generated ROS (for asbestos and silica) as NLRP3-activating mechanisms revealed parallel convergent pathways upstream of the inflammasome.

    Evidence Cathepsin B inhibition, lysosomal damage assays, NADPH oxidase inhibition, Nalp3 KO mice in inhalation model

    PMID:18403674 PMID:18604214

    Open questions at the time
    • Whether lysosomal and ROS pathways are redundant or additive not determined
    • Direct molecular interface between NLRP3 and these signals unknown
  6. 2009 High

    Defining NF-κB-dependent transcriptional induction of NLRP3 as a necessary priming step (Signal 1) that is insufficient without a second activation stimulus established the two-signal model of NLRP3 inflammasome activation.

    Evidence Reporter assays, NLRP3 knockdown/overexpression, macrophage stimulation

    PMID:19570822

    Open questions at the time
    • Post-translational priming events not yet distinguished from transcriptional priming
  7. 2010 High

    Localization of resting NLRP3 to ER membranes and its redistribution to perinuclear ER-mitochondria clusters upon activation, coupled with mitophagy-dependent regulation, placed mitochondrial integrity at the center of NLRP3 surveillance.

    Evidence Confocal/live-cell imaging, autophagy inhibition, VDAC inhibition in macrophages

    PMID:21124315

    Open questions at the time
    • Direct molecular tether between NLRP3 and mitochondria not identified at this stage
  8. 2012 High

    Discovery that BRCC3/BRISC-mediated deubiquitination of NLRP3 is required for inflammasome activation, and that TLR4 priming rapidly triggers NLRP3 deubiquitination, revealed post-translational licensing as a distinct priming mechanism beyond transcription.

    Evidence Ubiquitination assays, pharmacological deubiquitination inhibition, BRISC complex Co-IP

    PMID:22948162 PMID:23246432

    Open questions at the time
    • Specific ubiquitin chain types and lysine sites on NLRP3 not fully mapped
    • Relationship between ubiquitination and conformational change unclear
  9. 2013 High

    Demonstration that mitochondrial cardiolipin directly binds NLRP3 and is required for activation independently of ROS identified the first endogenous lipid ligand and a convergence point for ROS-dependent and -independent pathways.

    Evidence Direct cardiolipin-NLRP3 binding assay, cardiolipin synthesis inhibition

    PMID:23954133

    Open questions at the time
    • Binding site on NLRP3 for cardiolipin not mapped
    • Structural basis of lipid recognition unknown
  10. 2014 High

    Cryo-EM resolution of ASC PYD filaments showed that NLRP3 nucleates PYD filament assembly, which in turn clusters ASC CARDs to nucleate caspase-1 CARD filaments, establishing the hierarchical prion-like amplification mechanism of inflammasome signaling.

    Evidence Cryo-EM structure, structure-guided mutagenesis, filament reconstitution

    PMID:24630722

    Open questions at the time
    • Structure of oligomeric active NLRP3 itself not resolved
    • Stoichiometry of NLRP3 in the active complex unknown
  11. 2015 High

    Identification of MCC950 as a specific NLRP3 inhibitor effective against canonical and noncanonical pathways, and of the dopamine/cAMP/MARCH7 axis as a negative-regulatory degradation pathway, provided the first pharmacological tools and a physiological negative feedback circuit for NLRP3.

    Evidence Pharmacological inhibitor characterization with selectivity controls, cAMP-NLRP3 binding, MARCH7 ubiquitination assays, in vivo disease models

    PMID:25594175 PMID:25686105

    Open questions at the time
    • MCC950 binding site on NLRP3 not yet resolved at this point
    • cAMP binding site on NLRP3 not mapped
  12. 2016 High

    NEK7 was identified as an essential NLRP3-binding partner acting downstream of K⁺ efflux; NEK7 binds the NLRP3 catalytic domain independently of its own kinase activity and is required for NLRP3 oligomerization and activation.

    Evidence NEK7 KO hematopoietic chimera mice, Co-IP, mutational analysis

    PMID:26814970

    Open questions at the time
    • How K⁺ efflux licenses NEK7 binding unknown
    • Structural detail of NEK7-NLRP3 interface not available
  13. 2019 High

    The cryo-EM structure of the NLRP3-NEK7 complex revealed that NEK7's C-lobe contacts both NACHT and LRR domains and can bridge adjacent NLRP3 subunits; separately, MCC950's binding site was mapped to the Walker B motif in the NACHT ATPase domain, explaining its mechanism as an ATPase inhibitor.

    Evidence Cryo-EM at 3.8 Å, site-directed mutagenesis, direct MCC950-NLRP3 binding and ATPase assays

    PMID:31086327 PMID:31189953

    Open questions at the time
    • Structure represents inactive conformation only
    • Active oligomeric NLRP3 structure not determined
  14. 2019 High

    Human-specific alternative splicing producing an exon-5-deleted NLRP3 isoform that cannot bind NEK7 revealed a species-specific regulatory layer, and SUMOylation of NLRP3 at K204 by UBC9/SUMO1 was shown to facilitate ASC oligomerization.

    Evidence RT-PCR isoform analysis, NEK7 interaction assays, K204 mutagenesis, SUMOylation assays

    PMID:31324763 PMID:31914638

    Open questions at the time
    • Proportion of endogenous splice variants across tissues not quantified
    • How SUMOylation at K204 promotes ASC recruitment structurally unclear
  15. 2020 High

    A complex regulatory network converging on NLRP3 stability was delineated: AKT phosphorylation at S5 limits oligomerization while reducing Trim31-mediated K48-ubiquitination; UAF1/USP1 removes K48 chains to stabilize NLRP3; and STING promotes NLRP3 ER localization and attenuates ubiquitination during viral infection.

    Evidence Phospho-mutagenesis, chain-type-specific ubiquitination assays, Uaf1 KO macrophages, STING Co-IP and ER localization imaging

    PMID:32187211 PMID:32929041 PMID:33247121

    Open questions at the time
    • Temporal ordering of phosphorylation relative to deubiquitination during priming not resolved
    • Whether AKT-S5 and STING pathways intersect unknown
  16. 2021 High

    The cryo-EM structure of inactive full-length NLRP3 revealed a double-ring cage held by LRR–LRR contacts with sequestered PYD, localizing to membranes; structure-guided mutants defective in cage formation abolished TGN dispersion, ASC speck formation, and pyroptosis, demonstrating the cage is the pre-activation platform.

    Evidence Cryo-EM of endogenous full-length NLRP3, structure-guided mutagenesis, live-cell imaging of TGN dispersion

    PMID:34861190

    Open questions at the time
    • Transition mechanism from double-ring cage to active oligomer not captured structurally
    • How activating signals disassemble the cage unknown
  17. 2021 High

    Additional negative regulatory E3 ligases (ARIH2 via K48/K63 chains, β-TrCP1 via K27 chains blocked by YAP, gp78/Insig-1) and TRIM28-mediated SUMOylation that stabilizes NLRP3 by antagonizing ubiquitination expanded the PTM code governing NLRP3 levels and activity.

    Evidence CRISPR KO, chain-type ubiquitination assays, conditional KO mice, competitive binding (YAP/β-TrCP1), TRIM28 KO macrophages

    PMID:29021376 PMID:33976226 PMID:34373456 PMID:35110683

    Open questions at the time
    • Hierarchy and redundancy among multiple E3 ligases not determined
    • Whether different E3s target distinct NLRP3 pools (ER vs TGN) unknown
  18. 2022 High

    Covalent targeting of NLRP3 Cys598 by costunolide and direct binding of oxidized mitochondrial DNA by the pyrin domain refined the ligand-sensing model, while the caspase-11–NLRP3 pre-activation complex and Tau-mediated PYD acetylation at K21/K22/K24 expanded NLRP3's roles in noncanonical inflammasome activation and neurodegeneration.

    Evidence Mass spectrometry for covalent binding site, Ox-mtDNA binding IC50 measurements, caspase-11 Co-IP with KO controls, in vitro Tau acetylation assay with MS site identification

    PMID:35487985 PMID:36873170 PMID:37253813 PMID:38488468

    Open questions at the time
    • PYD domain serving both as DNA-binding and ASC-nucleating surface raises unresolved mutual exclusivity question
    • Physiological relevance of Tau acetyltransferase activity on NLRP3 requires independent replication
  19. 2023 High

    ZDHHC5 palmitoylation of the LRR domain and ZDHHC7 palmitoylation at Cys126 were identified as essential for NLRP3 TGN localization, NEK7 interaction, and inflammasome assembly, establishing palmitoylation as a critical lipid modification gating NLRP3 activation.

    Evidence Acyl-RAC palmitoylation assays, ZDHHC5/7 KO mice, Cys126 mutagenesis, live-cell TGN imaging

    PMID:38092000 PMID:38583156

    Open questions at the time
    • Full complement of palmitoylation sites across NLRP3 domains not exhaustively mapped
    • How palmitoylation integrates with the cage-to-active-oligomer transition structurally unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural transition from the membrane-bound double-ring cage to the active NEK7-bridged oligomer, the precise mechanism by which diverse stimuli converge to disassemble the cage, and the full integration of the multi-layered PTM code (ubiquitination, SUMOylation, palmitoylation, phosphorylation, acetylation) into a unified activation model remain unresolved.
  • No structure of the active NLRP3 oligomeric disc captured
  • Mechanism linking K⁺ efflux to NEK7 accessibility not identified
  • How palmitoylation, ubiquitination, and SUMOylation are temporally coordinated during activation is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140299 molecular sensor activity 5 GO:0060090 molecular adaptor activity 3 GO:0140657 ATP-dependent activity 2
Localization
GO:0005783 endoplasmic reticulum 2 GO:0005794 Golgi apparatus 2 GO:0005829 cytosol 2 GO:0031410 cytoplasmic vesicle 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-168256 Immune System 6 R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-1643685 Disease 3
Partners
BRCC3CASP1NEK7PYCARDRACK1TMEM173ZDHHC5ZDHHC7
Complex memberships
NLRP3 double-ring cageNLRP3 inflammasome

Evidence

Reading pass · 50 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 NLRP3 (CIAS1/cryopyrin) was identified as a novel gene encoding a protein with a pyrin domain, NACHT domain, and leucine-rich repeat (LRR) motif region; gain-of-function mutations cause familial cold autoinflammatory syndrome (FCAS) and Muckle-Wells syndrome (MWS), establishing its role in inflammatory regulation. Direct sequencing of genomic DNA from affected families; genetic mapping Nature genetics High 11687797
2004 NLRP3 (NALP3/cryopyrin) assembles an inflammasome complex with ASC, the CARD-containing protein Cardinal, and caspase-1 (but not caspase-5), forming a platform with high pro-IL-1β-processing activity; gain-of-function Muckle-Wells mutations cause spontaneous IL-1β secretion from macrophages. Co-immunoprecipitation, reconstitution of inflammasome complex, macrophage assays from MWS patients Immunity High 15030775
2006 NLRP3 (NALP3) inflammasome is activated by monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD) crystals, leading to caspase-1-dependent IL-1β and IL-18 production; macrophages deficient in caspase-1, ASC, or NALP3 are defective in crystal-induced IL-1β activation, and NLRP3-deficient mice show impaired neutrophil influx in crystal-induced peritonitis. Genetic knockout (caspase-1, ASC, NALP3 KO mice), in vivo peritonitis model, cytokine assays Nature High 16407889
2007 Activation of the NALP3 inflammasome requires low intracellular potassium concentration; inhibiting K+ efflux blocks NALP3 (but not IPAF) inflammasome activation, and in vitro NALP3 inflammasome assembly and caspase-1 recruitment occurs spontaneously at K+ concentrations below 90 mM. Pharmacological K+ efflux inhibition, in vitro reconstitution assay at defined K+ concentrations Cell death and differentiation High 17599094
2008 Silica crystals and aluminum salts activate the NALP3 inflammasome via a mechanism requiring phagocytosis, leading to lysosomal damage and rupture; cathepsin B release from lysosomes into the cytoplasm is required for NALP3 activation. Sterile lysosomal damage alone suffices to activate NALP3. Genetic KO macrophages, pharmacological inhibition of cathepsin B and phagosomal acidification, lysosomal damage assays Nature immunology High 18604214
2008 Asbestos and silica particles are sensed by the Nalp3 inflammasome; NADPH oxidase-generated reactive oxygen species upon particle phagocytosis trigger inflammasome activation and IL-1β secretion; Nalp3−/− mice show reduced inflammatory cell recruitment and cytokine production in an asbestos inhalation model. Nalp3 KO mice, in vivo inhalation model, ROS inhibition assays Science High 18403674
2009 NF-κB-activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by inducing NLRP3 expression as a critical checkpoint; NF-κB activation is necessary but not sufficient for NLRP3 activation — a second stimulus (ATP or crystal-induced damage) is also required. Reporter assays, NLRP3 expression knockdown/overexpression, macrophage stimulation assays Journal of immunology High 19570822
2010 Resting NLRP3 localizes to endoplasmic reticulum structures; upon inflammasome activation, both NLRP3 and ASC redistribute to the perinuclear space where they co-localize with ER and mitochondria clusters. Mitophagy/autophagy blockade leads to accumulation of damaged, ROS-generating mitochondria that activate the NLRP3 inflammasome; voltage-dependent anion channel inhibition suppresses both ROS generation and inflammasome activation. Confocal microscopy/live imaging, autophagy inhibition, VDAC inhibition, genetic KO macrophages Nature High 21124315
2010 Cholesterol crystals activate the NLRP3 inflammasome in human macrophages via lysosomal destabilization and cathepsin B release; siRNA silencing of NLRP3 abolishes crystal-induced IL-1β secretion, establishing NLRP3 as the cholesterol crystal-sensing element. siRNA knockdown, cathepsin B inhibition, lysosomal permeability assays, IL-1β ELISA PloS one High 20668705
2011 The NLRP3 inflammasome senses lipotoxicity-associated increases in intracellular ceramide to induce caspase-1 cleavage in macrophages and adipose tissue; Nlrp3 ablation in mice prevents obesity-induced inflammasome activation in fat depots and liver and enhances insulin signaling. Nlrp3 KO mice, ceramide treatment assays, adipose tissue caspase-1 and IL-18 measurements Nature medicine High 21217695
2012 NLRP3 is activated in Alzheimer's disease; NLRP3-deficient (Nlrp3−/−) and Casp1−/− mice carrying familial AD mutations are largely protected from spatial memory loss, show reduced caspase-1 and IL-1β activation in brain, enhanced amyloid-β clearance, and a shift of microglia to M2 phenotype with decreased amyloid-β deposition. Nlrp3/Casp1 KO mouse models of AD, behavioral testing, immunohistochemistry, cytokine assays Nature High 23254930
2012 BRCC3 (a deubiquitinating enzyme in the cytosolic BRISC complex) critically regulates NLRP3 activity by promoting its deubiquitination; NLRP3 is a substrate for BRCC3-containing BRISC complex, and its ubiquitination status controls inflammasome activation. Co-immunoprecipitation, pharmacological and molecular (siRNA/overexpression) approaches, ubiquitination assays Molecular cell High 23246432
2012 TLR4/MyD88 signaling can rapidly and non-transcriptionally prime NLRP3 by stimulating its deubiquitination, dependent on mitochondrial ROS; ATP signaling also induces NLRP3 deubiquitination independently of ROS; pharmacological inhibition of NLRP3 deubiquitination blocks NLRP3 activation, demonstrating that deubiquitination is required for NLRP3 activation. Ubiquitination assays, ROS inhibition, pharmacological deubiquitination inhibition, macrophage stimulation assays Journal of biological chemistry High 22948162
2012 PKR (double-stranded RNA-dependent protein kinase) physically interacts with NLRP3, NLRP1, NLRC4, and AIM2 and is required for inflammasome activation; PKR autophosphorylation in a cell-free system with recombinant NLRP3, ASC, and pro-caspase-1 reconstitutes inflammasome activity. Co-immunoprecipitation, PKR KO macrophages, cell-free reconstitution with recombinant proteins Nature High 22801494
2013 Mitochondrial cardiolipin directly binds NLRP3 and is required for Nlrp3 inflammasome activation; interference with cardiolipin synthesis specifically inhibits Nlrp3 inflammasome activation independently of ROS, identifying cardiolipin as a convergence point for ROS-dependent and ROS-independent Nlrp3 activation pathways. Direct binding assay (cardiolipin-NLRP3 interaction), cardiolipin synthesis inhibition, linezolid as ROS-independent Nlrp3 agonist Immunity High 23954133
2014 ASC forms filaments upon inflammasome activation; activated NLRP3 nucleates PYD filaments of ASC, which in turn cluster the CARD of ASC to nucleate CARD filaments of caspase-1, leading to proximity-induced caspase-1 activation. Cryo-EM structure of ASC(PYD) filament at near-atomic resolution provides a template for homo- and hetero-PYD/PYD associations. Cryo-EM structure determination, structure-guided mutagenesis, filament assembly assays Cell High 24630722
2014 Aryl hydrocarbon receptor (AhR) negatively regulates NLRP3 expression by binding to xenobiotic response elements (XRE) in the NLRP3 promoter and inhibiting NLRP3 transcription; AhR activation suppresses caspase-1 activation and IL-1β secretion in peritoneal macrophages and alum-induced peritonitis in vivo. ChIP assay, siRNA knockdown, luciferase reporter assay, macrophage and in vivo peritonitis assays Nature communications High 25141024
2015 MCC950, a potent small-molecule inhibitor, selectively inhibits NLRP3 but not AIM2, NLRC4, or NLRP1 inflammasomes at nanomolar concentrations, blocking canonical and noncanonical NLRP3 activation; MCC950 reduces IL-1β production in vivo and rescues neonatal lethality in a CAPS mouse model. Pharmacological inhibitor characterization, KO controls for specificity, in vivo EAE and CAPS models Nature medicine High 25686105
2015 Dopamine inhibits NLRP3 inflammasome activation via dopamine D1 receptor (DRD1) signaling; DRD1 signaling increases cAMP, which binds to NLRP3 and promotes its ubiquitination and degradation via the E3 ubiquitin ligase MARCH7. Co-immunoprecipitation, cAMP binding assay, ubiquitination assays, DRD1 KO mice, in vivo neuroinflammation and peritonitis models Cell High 25594175
2015 Small heterodimer partner (SHP) is a negative regulator of NLRP3 inflammasome activation; SHP interacts with NLRP3 at mitochondria, competitively inhibiting NLRP3 binding to ASC; SHP deficiency leads to accumulation of damaged mitochondria and sustained NLRP3-ASC interaction at the ER. Co-immunoprecipitation, overexpression competition assay, SHP KO macrophages, confocal microscopy, mouse models Nature communications High 25655831
2016 NEK7, a mammalian NIMA-related kinase, is an essential NLRP3-binding protein that acts downstream of potassium efflux to regulate NLRP3 oligomerization and activation; NLRP3 associates with the catalytic domain of NEK7, but NEK7 kinase activity is dispensable; NEK7 deficiency abrogates caspase-1 activation and IL-1β release in response to NLRP3 (but not NLRC4 or AIM2) stimuli; NEK7 is required for CAPS-associated NLRP3 mutant activation. Co-immunoprecipitation, NEK7 KO mice (hematopoietic chimeras), mutational analysis, high-molecular-mass complex analysis Nature High 26814970
2017 ARIH2 (E3 ubiquitin ligase) interacts with NLRP3 via its NACHT domain and ubiquitinates NLRP3 via K48- and K63-linked chains through its RING2 domain, negatively regulating NLRP3 inflammasome activation; CRISPR/Cas9 deletion of endogenous ARIH2 promotes NLRP3 inflammasome activation. Co-immunoprecipitation, ubiquitination assays with ARIH2 mutants, CRISPR/Cas9 KO, overexpression studies Journal of immunology High 29021376
2019 MCC950 directly interacts with the Walker B motif within the NLRP3 NACHT domain, blocking ATP hydrolysis and inhibiting NLRP3 activation and inflammasome formation. Direct binding assay, ATPase activity assay, mutagenesis of Walker B motif Nature chemical biology High 31086327
2019 Cryo-EM structure of inactive human NLRP3 in complex with NEK7 at 3.8 Å resolution reveals that the C-terminal lobe of NEK7 nestles against both the LRR and NACHT domains of NLRP3; modeling predicts NEK7 bridges adjacent NLRP3 subunits with bipartite interactions to mediate activation; interface mutations abolish NEK7- or NLRP3-rescue of inflammasome activation in KO cells. Cryo-EM structure determination, site-directed mutagenesis, KO cell rescue assays Nature High 31189953
2019 Human NLRP3, but not mouse NLRP3, undergoes alternative splicing producing a major isoform lacking exon 5; the exon-5-deleted isoform lacks the interaction surface for NEK7 and therefore lacks inflammasome activity, revealing a stochastic regulatory role for alternative splicing of NLRP3 LRR domain. RT-PCR isoform characterization, NEK7 interaction assays with splice variants, functional caspase-1 assays Nature communications High 31324763
2020 AKT associates with NLRP3 and phosphorylates it on serine 5 (S5), limiting NLRP3 oligomerization; S5 phosphorylation also stabilizes NLRP3 by reducing its ubiquitination on lysine 496, inhibiting proteasome-mediated degradation by the E3 ligase Trim31; dephosphorylation of S5 by PP2A allows NLRP3 activation. Co-immunoprecipitation, phospho-specific mutagenesis, ubiquitination assays, pharmacological AKT manipulation, in vivo LPS model Journal of immunology High 32929041
2020 STING binds to NLRP3 upon HSV-1 infection and promotes NLRP3 localization to the endoplasmic reticulum, facilitating inflammasome formation; STING also attenuates K48- and K63-linked polyubiquitination of NLRP3, promoting inflammasome activation. Co-immunoprecipitation, confocal microscopy (ER co-localization), ubiquitination assays, siRNA knockdown, primary cells and mouse models PLoS pathogens High 32187211
2020 RACK1 interacts with NLRP3 and NEK7 (but not ASC) in macrophages and promotes the active conformation of NLRP3 induced by activating stimuli, facilitating subsequent inflammasome assembly; RACK1 suppression specifically abrogates caspase-1 activation in response to NLRP3 (but not NLRC4 or AIM2) stimuli, independently of RACK1's ribosomal binding activity. Co-immunoprecipitation, siRNA knockdown, conformational assays, NLRC4/AIM2 selectivity controls Cell reports High 33207200
2020 UAF1/USP1 deubiquitinase complex selectively removes K48-linked polyubiquitination from NLRP3, suppressing its degradation and increasing cellular NLRP3 levels required for inflammasome assembly; UAF1/USP12 and UAF1/USP46 complexes promote NF-κB activation by deubiquitinating p65, enhancing NLRP3 and pro-IL-1β transcription. Co-immunoprecipitation, ubiquitination chain-type assays, Uaf1 KO macrophages, in vivo assays Nature communications High 33247121
2021 Full-length mouse NLRP3 forms a 12- to 16-mer double-ring cage held together by LRR-LRR interactions, with pyrin domains shielded within the assembly to prevent premature activation; this NLRP3 form is predominantly membrane-localized. Trans-Golgi network dispersion into vesicles (an early event for many NLRP3-activating stimuli) requires the double-ring cages; double-ring-defective NLRP3 mutants abolish inflammasome punctum formation, caspase-1 processing, and cell death. Cryo-EM structure of endogenous full-length NLRP3, structure-guided mutagenesis, membrane fractionation, live-cell imaging of TGN dispersion Cell High 34861190
2021 TRIM28 (E3 SUMO ligase) binds NLRP3 and promotes SUMO1, SUMO2, and SUMO3 modification of NLRP3, thereby inhibiting NLRP3 ubiquitination and proteasomal degradation and stabilizing NLRP3 protein; Trim28 deficiency attenuates NLRP3 inflammasome activation in vitro and in vivo. Co-immunoprecipitation, SUMOylation assays, ubiquitination assays, Trim28 KO macrophages and mice Nature communications High 34373456
2021 YAP physically interacts with NLRP3 and maintains NLRP3 stability by blocking the association between NLRP3 and the E3 ligase β-TrCP1; β-TrCP1 promotes proteasomal degradation of NLRP3 via K27-linked ubiquitination at Lys380; YAP deficiency in myeloid cells attenuates LPS-induced systemic inflammation and MSU-induced peritonitis. Co-immunoprecipitation, ubiquitination assays (chain-type specific), YAP conditional KO mice, in vivo peritonitis model Nature communications High 33976226
2021 USP5 promotes autophagic degradation of NLRP3, attenuating NLRP3 inflammasome activation; USP5 interacts with NLRP3 and promotes its K63-linked deubiquitination, facilitating MARCHF7/MARCH7-mediated autophagy-dependent NLRP3 degradation. Co-immunoprecipitation, ubiquitination assays, autophagy flux assays (3-MA, BafA1, CQ), KD experiments Autophagy Medium 34486483
2021 Pharmacological inhibition of BRCC3 (JAMM domain metalloprotease) by thiolutin (THL) blocks NLRP3 inflammasome activation by preventing BRISC-mediated NLRP3 deubiquitination; THL potently inhibits canonical, noncanonical, alternative, and transcription-independent NLRP3 activation pathways at nanomolar concentrations and is effective in multiple mouse inflammatory disease models. Pharmacological inhibitor (THL), BRISC deubiquitination assays, multiple KO controls, in vivo mouse models Science immunology High 33931568
2019 SUMO1 catalyzes SUMOylation of NLRP3 at residue Lys204 (via UBC9), facilitating ASC oligomerization and inflammasome activation; SENP3 deSUMOylates NLRP3, attenuating ASC recruitment and speck formation and IL-1β cleavage. Co-immunoprecipitation, site-directed mutagenesis (Lys204), SUMOylation assays, SENP3 overexpression/knockdown FASEB journal High 31914638
2022 The caspase-11–NLRP3 interaction (before caspase-11 activation) is required for noncanonical NLRP3 inflammasome activation; concurrent detection of bacterial RNA by NLRP3 and LPS binding by pro-caspase-11 mediates this interaction, nucleating a scaffold for their interdependent activation. Co-immunoprecipitation, genetic KO macrophages (Casp11, Nlrp3), mechanistic reconstitution with bacterial mRNA/LPS Nature immunology High 35487985
2022 NLRP3 Cys598 in the NACHT domain is the direct covalent binding site for costunolide (COS), which alters NLRP3 ATPase activity and inhibits inflammasome assembly; the α-methylene-γ-butyrolactone motif in COS is the active group for NLRP3 inhibition. Covalent binding site identification (mass spectrometry/mutagenesis), ATPase activity assay, macrophage and disease model assays Acta pharmaceutica Sinica B High 36873170
2022 Ubiquitination of NLRP3 by gp78 (membrane-bound E3 ubiquitin ligase) inhibits NLRP3 inflammasome activation by suppressing NLRP3 oligomerization and subcellular translocation; Insig-1 (ER membrane protein) is required for the gp78-NLRP3 interaction and gp78-mediated NLRP3 ubiquitination; gp78 or Insig-1 myeloid-specific deficiency exacerbates NLRP3-dependent inflammation in vivo. Co-immunoprecipitation, ubiquitination assays, myeloid-specific KO mice, in vivo inflammation models Cell death and differentiation High 35110683
2022 Tau protein acts as an acetyltransferase that directly acetylates NLRP3 at K21, K22, and K24 in the PYD domain, inducing inflammasome activation in microglia; phosphorylated Tau species promote NLRP3 acetylation-dependent inflammasome activation; blocking the Tau-NLRP3 interaction with a peptide inhibits NLRP3 acetylation, microgliosis, and cognitive impairment in mice. In vitro acetylation assay, Co-IP, mass spectrometry (acetylation sites), mutant Tau constructs, AAV mouse model, behavioral testing Clinical and translational medicine High 38488468
2022 Deletion of the NLRP3 LRR domain inhibits NLRP3 self-association, oligomerization, and interaction with NEK7, and diminishes inflammasome activation in macrophages; this was shown using endogenous NLRP3 mutant knock-in mice and reconstitution of NLRP3-deficient macrophages. NLRP3 LRR deletion knock-in mice, NLRP3-deficient macrophage reconstitution, oligomerization assays, NEK7 Co-IP Journal of biological chemistry High 36403854
2022 NLRP3 directly binds non-oxidized and oxidized mitochondrial DNA (Ox-mtDNA) with differential affinity (IC50 ~4 nM for non-oxidized vs ~247 nM for Ox-mtDNA); the NLRP3 pyrin domain mediates DNA binding and prefers Ox-mtDNA; NOMIDFCAS gain-of-function NLRP3 mutant has higher affinity for Ox-mtDNA. Direct binding assay (IC50 determination), pyrin domain deletion and isolation binding assays, monoclonal antibody blocking assay, structural modeling Communications biology Medium 37253813
2023 ZDHHC5 palmitoylates NLRP3 at the LRR domain, promoting NLRP3 oligomerization, NLRP3-NEK7 interaction, and formation of large ASC aggregates leading to caspase-1 activation; ABHD17A depalmitoylates NLRP3; Zdhhc5−/− mice show defective NLRP3 inflammasome activation in vivo; a human heritable disease-associated NLRP3 mutation is associated with defective ABHD17A binding and hyper-palmitoylation. Palmitoylation assays (acyl-RAC), ZDHHC5 KO cells and Zdhhc5−/− mice, Co-IP (NLRP3-NEK7), ASC speck formation assays, disease mutation analysis Molecular cell High 38092000
2024 ZDHHC7 palmitoylates NLRP3 at Cys126, which is critical for NLRP3-mediated inflammasome activation; Cys126 palmitoylation promotes resting NLRP3 localization on the trans-Golgi network (TGN) and activated NLRP3 on dispersed TGN, indispensable for ASC recruitment and oligomerization; ZDHHC12 has an opposing termination effect; ZDHHC7 KO diminishes NLRP3 activation in vivo. Palmitoylation assays, ZDHHC7 KO macrophages and mice, Cys126 mutagenesis, TGN localization by live-cell imaging/fractionation, ASC oligomerization assays Cell reports High 38583156
2008 Initial characterization of the human NLRP3 promoter identified two transcriptional start sites, three 5'-UTR splice forms, potential promoter regions, and six new DNA promoter variants; one variant unique to a mutation-negative cryopyrinopathy patient increases in vitro gene expression. 5'-RACE, promoter deletion/reporter assays, sequencing of patient DNA Genes and immunity Medium 18719602
2016 TIFA regulates both priming (signal 1) and activation (signal 2) of NLRP3 inflammasome in endothelial cells; TIFA Thr9 phosphorylation by AKT drives TIFA oligomerization, which facilitates higher-order NLRP3 inflammasome assembly via TIFA-caspase-1 interaction; sterol regulatory element-binding protein 2 transactivates TIFA to induce NF-κB-dependent NLRP3 transcription. Co-immunoprecipitation (TIFA-caspase-1), mutagenesis (Thr9), ChIP, siRNA knockdown, atheroprone flow model PNAS Medium 27965388
2020 Activated NLRP3 inflammasome (ASC pyroptosome) universally localizes within the cytoplasm rather than with specific organelles under ATP, nigericin, or MSU stimulation in mouse peritoneal macrophages; endogenous ASC co-localizes with NLRP3 and caspase-1 in cytoplasmic specks but not with mitochondria, ER, Golgi, or other organelles screened. Confocal microscopy of endogenous proteins, co-localization with 8 organelle markers under multiple stimuli Protein & cell Medium 23609011
2020 β-catenin physically interacts with NLRP3 and promotes the association between NLRP3 and ASC; siRNA suppression of β-catenin or pharmacological inhibition impairs NLRP3 inflammasome activation and attenuates LPS-induced systemic inflammation in vivo. Co-immunoprecipitation, siRNA knockdown, β-catenin inhibitor, in vivo LPS model Molecular immunology Medium 32244067
2021 USP22 promotes NLRP3 degradation and inhibits NLRP3 inflammasome activation via promotion of ATG5-mediated macroautophagy; USP22 stabilizes ATG5 by decreasing K27- and K48-linked ubiquitination of ATG5 at Lys118, thereby indirectly promoting autophagic NLRP3 degradation. Co-immunoprecipitation, ubiquitination assays, autophagy flux assays, USP22 KD mice, in vivo peritonitis/inflammation models Autophagy Medium 35900990
2021 TRIM31 interacts with NLRP3 in retinal pigment epithelial cells and promotes NLRP3 ubiquitination, inhibiting NLRP3 inflammasome activation and pyroptosis. Co-immunoprecipitation, ubiquitination assay, TRIM31 overexpression/knockdown, inflammasome activation assays Cell biology international Medium 32716108
2021 Licochalcone B (LicoB) directly binds NEK7 and inhibits the NLRP3-NEK7 interaction, thereby suppressing NLRP3 inflammasome activation specifically (not AIM2 or NLRC4); LicoB is protective in mouse models of NLRP3-driven diseases. Direct binding assay (LicoB-NEK7), Co-IP (NLRP3-NEK7 disruption), selectivity assays, mouse disease models EMBO reports High 34882936

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 A role for mitochondria in NLRP3 inflammasome activation. Nature 4626 21124315
2006 Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 4145 16407889
2009 Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. Journal of immunology (Baltimore, Md. : 1950) 2467 19570822
2008 Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nature immunology 2415 18604214
2015 A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nature medicine 2295 25686105
2012 NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature 2289 23254930
2016 Mechanism and Regulation of NLRP3 Inflammasome Activation. Trends in biochemical sciences 2273 27669650
2011 The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nature medicine 2134 21217695
2009 AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 2117 19158675
2008 Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science (New York, N.Y.) 2104 18403674
2015 Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion. Cell research 2071 26611636
2012 Inflammasomes in health and disease. Nature 1834 22258606
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2004 NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity 1452 15030775
2001 Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nature genetics 1304 11687797
2007 Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. Cell death and differentiation 1169 17599094
2014 Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes. Cell 1140 24630722
2016 NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux. Nature 1063 26814970
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2015 Dopamine controls systemic inflammation through inhibition of NLRP3 inflammasome. Cell 849 25594175
2019 MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition. Nature chemical biology 812 31086327
2010 Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: a novel link between cholesterol metabolism and inflammation. PloS one 797 20668705
2003 NODs: intracellular proteins involved in inflammation and apoptosis. Nature reviews. Immunology 776 12766759
2013 Mitochondrial cardiolipin is required for Nlrp3 inflammasome activation. Immunity 771 23954133
2009 Glyburide inhibits the Cryopyrin/Nalp3 inflammasome. The Journal of cell biology 699 19805629
2021 Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients. The Journal of experimental medicine 657 33231615
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2019 Structural mechanism for NEK7-licensed activation of NLRP3 inflammasome. Nature 644 31189953
2012 Novel role of PKR in inflammasome activation and HMGB1 release. Nature 639 22801494
2012 Non-transcriptional priming and deubiquitination regulate NLRP3 inflammasome activation. The Journal of biological chemistry 635 22948162
2014 Mechanism of NLRP3 inflammasome activation. Annals of the New York Academy of Sciences 595 24840700
2012 Deubiquitination of NLRP3 by BRCC3 critically regulates inflammasome activity. Molecular cell 582 23246432
2020 Interplay Between NLRP3 Inflammasome and Autophagy. Frontiers in immunology 492 33163006
2020 NLRP3 inflammasome in endothelial dysfunction. Cell death & disease 394 32948742
1990 Functional studies of nonpeptide angiotensin II receptor subtype-specific ligands: DuP 753 (AII-1) and PD123177 (AII-2). The Journal of pharmacology and experimental therapeutics 323 2243344
2020 NLRP3 Inflammasome and Inflammatory Diseases. Oxidative medicine and cellular longevity 288 32148650
2011 Differential expression of NLRP3 among hematopoietic cells. Journal of immunology (Baltimore, Md. : 1950) 275 21257968
2018 Metabolic regulation of NLRP3. Immunological reviews 250 29247992
2018 Spotlight on the NLRP3 inflammasome pathway. Journal of inflammation research 216 30288079
2021 NLRP3 cages revealed by full-length mouse NLRP3 structure control pathway activation. Cell 211 34861190
2020 STING promotes NLRP3 localization in ER and facilitates NLRP3 deubiquitination to activate the inflammasome upon HSV-1 infection. PLoS pathogens 187 32187211
2018 Regulation of NLRP3 Inflammasome by Phosphorylation. Frontiers in immunology 187 30349539
2014 Aryl hydrocarbon receptor negatively regulates NLRP3 inflammasome activity by inhibiting NLRP3 transcription. Nature communications 187 25141024
2023 Pharmacological Inhibition of the NLRP3 Inflammasome: Structure, Molecular Activation, and Inhibitor-NLRP3 Interaction. Pharmacological reviews 162 36669831
2009 Dopamine-stimulated dephosphorylation of connexin 36 mediates AII amacrine cell uncoupling. The Journal of neuroscience : the official journal of the Society for Neuroscience 149 19940186
1993 Inhibition of rabbit aortic angiotensin II (AII) receptor by CV-11974, a new nonpeptide AII antagonist. Biochemical pharmacology 149 8347154
2012 Intrinsic properties and functional circuitry of the AII amacrine cell. Visual neuroscience 145 22310372
2018 NLRP3 inflammasome activation in inflammaging. Seminars in immunology 137 30268598
1992 Regulation of Na+ channels in the cortical collecting duct by AVP and mineralocorticoids. Kidney international 136 1313121
1984 Human apolipoproteins AI, AII, CII and CIII. cDNA sequences and mRNA abundance. Nucleic acids research 136 6328445
2021 YAP promotes the activation of NLRP3 inflammasome via blocking K27-linked polyubiquitination of NLRP3. Nature communications 129 33976226
2021 TRIM28 SUMOylates and stabilizes NLRP3 to facilitate inflammasome activation. Nature communications 129 34373456
2015 Small heterodimer partner interacts with NLRP3 and negatively regulates activation of the NLRP3 inflammasome. Nature communications 124 25655831
2017 ARIH2 Ubiquitinates NLRP3 and Negatively Regulates NLRP3 Inflammasome Activation in Macrophages. Journal of immunology (Baltimore, Md. : 1950) 116 29021376
2021 USP5 attenuates NLRP3 inflammasome activation by promoting autophagic degradation of NLRP3. Autophagy 112 34486483
2020 UAF1 deubiquitinase complexes facilitate NLRP3 inflammasome activation by promoting NLRP3 expression. Nature communications 111 33247121
2023 ZDHHC5-mediated NLRP3 palmitoylation promotes NLRP3-NEK7 interaction and inflammasome activation. Molecular cell 110 38092000
2002 Apolipoprotein A-II, HDL metabolism and atherosclerosis. Atherosclerosis 110 12119188
2016 Fluoxetine Inhibits NLRP3 Inflammasome Activation: Implication in Depression. The international journal of neuropsychopharmacology 106 27207922
2015 Sodium butyrate alleviates adipocyte inflammation by inhibiting NLRP3 pathway. Scientific reports 102 26234821
2019 Interaction between autophagy and the NLRP3 inflammasome. Acta biochimica et biophysica Sinica 101 31609412
2022 NLRP3 inflammasome in neurodegenerative disease. Translational research : the journal of laboratory and clinical medicine 97 35952982
2020 Inhibiting the NLRP3 Inflammasome. Molecules (Basel, Switzerland) 88 33255820
2022 Caspase-11 interaction with NLRP3 potentiates the noncanonical activation of the NLRP3 inflammasome. Nature immunology 87 35487985
2021 Licochalcone B specifically inhibits the NLRP3 inflammasome by disrupting NEK7-NLRP3 interaction. EMBO reports 82 34882936
2014 The AII amacrine cell connectome: a dense network hub. Frontiers in neural circuits 80 25237297
2021 NLRP3 Ubiquitination-A New Approach to Target NLRP3 Inflammasome Activation. International journal of molecular sciences 79 34445484
2004 Function and plasticity of homologous coupling between AII amacrine cells. Vision research 78 15535997
2020 Increasing complexity of NLRP3 inflammasome regulation. Journal of leukocyte biology 77 32531835
2018 Flavonoids interfere with NLRP3 inflammasome activation. Toxicology and applied pharmacology 77 29960001
2022 Salidroside Ameliorates Depression by Suppressing NLRP3-Mediated Pyroptosis via P2X7/NF-κB/NLRP3 Signaling Pathway. Frontiers in pharmacology 76 35496273
2022 Corilagin Restrains NLRP3 Inflammasome Activation and Pyroptosis through the ROS/TXNIP/NLRP3 Pathway to Prevent Inflammation. Oxidative medicine and cellular longevity 76 36299604
2007 Calcium-sensing receptor attenuates AVP-induced aquaporin-2 expression via a calmodulin-dependent mechanism. Journal of the American Society of Nephrology : JASN 75 18032798
2024 NLRP3 Cys126 palmitoylation by ZDHHC7 promotes inflammasome activation. Cell reports 71 38583156
2022 Costunolide covalently targets NACHT domain of NLRP3 to inhibit inflammasome activation and alleviate NLRP3-driven inflammatory diseases. Acta pharmaceutica Sinica. B 71 36873170
2021 Pharmacological targeting of NLRP3 deubiquitination for treatment of NLRP3-associated inflammatory diseases. Science immunology 69 33931568
2021 Roles of Neuropeptides, VIP and AVP, in the Mammalian Central Circadian Clock. Frontiers in neuroscience 67 33935635
2020 AKT Regulates NLRP3 Inflammasome Activation by Phosphorylating NLRP3 Serine 5. Journal of immunology (Baltimore, Md. : 1950) 67 32929041
2002 Fine structure mapping of CIAS1: identification of an ancestral haplotype and a common FCAS mutation, L353P. Human genetics 66 12522564
2022 USP22 suppresses the NLRP3 inflammasome by degrading NLRP3 via ATG5-dependent autophagy. Autophagy 62 35900990
2020 RACK1 Mediates NLRP3 Inflammasome Activation by Promoting NLRP3 Active Conformation and Inflammasome Assembly. Cell reports 62 33207200
2023 Targeting NLRP3 inflammasome for neurodegenerative disorders. Molecular psychiatry 58 37670126
2017 Apolipoprotein A-II alters the proteome of human lipoproteins and enhances cholesterol efflux from ABCA1. Journal of lipid research 58 28476857
2019 SUMO1 SUMOylates and SENP3 deSUMOylates NLRP3 to orchestrate the inflammasome activation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 57 31914638
1995 Expression cloning of an AVP-activated, calcium-mobilizing receptor from rabbit kidney medulla. The American journal of physiology 57 7611460
1983 Metabolism of human apolipoproteins A-I and A-II: compartmental models. Journal of lipid research 57 6403641
2009 MEFV, TNF1rA, CARD15 and NLRP3 mutation analysis in PFAPA. Rheumatology international 56 19579027
2022 Ubiquitination of NLRP3 by gp78/Insig-1 restrains NLRP3 inflammasome activation. Cell death and differentiation 55 35110683
2019 Alternative splicing regulates stochastic NLRP3 activity. Nature communications 55 31324763
2018 Copper Regulates the Canonical NLRP3 Inflammasome. Journal of immunology (Baltimore, Md. : 1950) 51 29358279
2014 Methylsulfonylmethane inhibits NLRP3 inflammasome activation. Cytokine 50 25461402
2022 NLRP3 inflammasome and NLRP3-related autoinflammatory diseases: From cryopyrin function to targeted therapies. Frontiers in immunology 49 36275641
2020 NLRC4 inflammasome activation is NLRP3- and phosphorylation-independent during infection and does not protect from melanoma. The Journal of experimental medicine 49 32342103
2002 Apolipoproteins A-I and A-II downregulate neutrophil functions. Lipids 48 12458630
2021 NLRP3 inflammasome in sepsis (Review). Molecular medicine reports 46 33982766
2016 TIFA as a crucial mediator for NLRP3 inflammasome. Proceedings of the National Academy of Sciences of the United States of America 44 27965388
2022 Depression compromises antiviral innate immunity via the AVP-AHI1-Tyk2 axis. Cell research 43 35821088
2020 The NLRP3 Inflammasome and Its Role in T1DM. Frontiers in immunology 43 32973739
2012 Electrical synapses between AII amacrine cells in the retina: Function and modulation. Brain research 41 22776293
2008 Initial description of the human NLRP3 promoter. Genes and immunity 41 18719602
2023 Differential Binding of NLRP3 to non-oxidized and Ox-mtDNA mediates NLRP3 Inflammasome Activation. Communications biology 40 37253813
2013 Cellular localization of NLRP3 inflammasome. Protein & cell 40 23609011
2020 Role of NLRP3 Inflammasomes in Neuroinflammation Diseases. European neurology 39 33202405
2015 The NLRP3 inflammasome and stroke. International journal of clinical and experimental medicine 39 26131053
2021 Suppression of lncRNA NLRP3 inhibits NLRP3-triggered inflammatory responses in early acute lung injury. Cell death & disease 37 34599154
2016 Goldfish Leptin-AI and Leptin-AII: Function and Central Mechanism in Feeding Control. International journal of molecular sciences 37 27249000
2004 Apolipoprotein A-II, genetic variation on chromosome 1q21-q24, and disease susceptibility. Current opinion in lipidology 37 15166779
2021 Oscillating lncRNA Platr4 regulates NLRP3 inflammasome to ameliorate nonalcoholic steatohepatitis in mice. Theranostics 36 33391484
2021 Research Progress of Mitochondrial Mechanism in NLRP3 Inflammasome Activation and Exercise Regulation of NLRP3 Inflammasome. International journal of molecular sciences 34 34639204
2020 β-catenin promotes NLRP3 inflammasome activation via increasing the association between NLRP3 and ASC. Molecular immunology 34 32244067
2019 Effects of phosphorylation on the NLRP3 inflammasome. Archives of biochemistry and biophysics 34 30844378
1996 ACTH and AII differentially stimulate steroid hormone orphan receptor mRNAs in adrenal cortical cells. Molecular and cellular endocrinology 34 9027329
2020 TRIM31 inhibits NLRP3 inflammasome and pyroptosis of retinal pigment epithelial cells through ubiquitination of NLRP3. Cell biology international 33 32716108
2006 AVP receptor antagonists as aquaretics: review and assessment of clinical data. Cleveland Clinic journal of medicine 33 16970150
2003 AII amacrine cells express the MT1 melatonin receptor in human and macaque retina. Experimental eye research 33 12907170
2021 Targeting the NLRP3 Inflammasome via BTK. Frontiers in cell and developmental biology 32 33718366
2019 microRNA-520c-3p suppresses NLRP3 inflammasome activation and inflammatory cascade in preeclampsia by downregulating NLRP3. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 32 31143973
1996 Cardiac effects of AII. AT1A receptor signaling, desensitization, and internalization. Advances in experimental medicine and biology 32 8726686
2024 Tau induces inflammasome activation and microgliosis through acetylating NLRP3. Clinical and translational medicine 31 38488468
2023 Natural products modulate NLRP3 in ulcerative colitis. Frontiers in pharmacology 31 37849728
2017 Nanoparticle fullerol alleviates radiculopathy via NLRP3 inflammasome and neuropeptides. Nanomedicine : nanotechnology, biology, and medicine 31 28404518
2001 Norepinephrine-induced CRH and AVP gene transcription within the hypothalamus: differential regulation by corticosterone. Brain research. Molecular brain research 31 11295232
2022 NLRP3: Role in ischemia/reperfusion injuries. Frontiers in immunology 30 36238294
2019 NLRP3 Inflammasome in Cardioprotective Signaling. Journal of cardiovascular pharmacology 30 31356546
2014 Polycomb binding precedes early-life stress responsive DNA methylation at the Avp enhancer. PloS one 29 24599304
2023 Atranorin inhibits NLRP3 inflammasome activation by targeting ASC and protects NLRP3 inflammasome-driven diseases. Acta pharmacologica Sinica 28 36964308
2017 Prox1 Is a Marker for AII Amacrine Cells in the Mouse Retina. Frontiers in neuroanatomy 28 28529477
2022 The leucine-rich repeat (LRR) domain of NLRP3 is required for NLRP3 inflammasome activation in macrophages. The Journal of biological chemistry 27 36403854
2021 A metabolically stable apelin-17 analog decreases AVP-induced antidiuresis and improves hyponatremia. Nature communications 27 33436646
2020 Modulatory mechanisms of NLRP3: Potential roles in inflammasome activation. Life sciences 27 33352170