Ask about this productRelated genes to: NLRP1 Blocking Peptide
- Gene:
- NLRP1 NIH gene
- Name:
- NLR family pyrin domain containing 1
- Previous symbol:
- NALP1, SLEV1
- Synonyms:
- KIAA0926, DKFZp586O1822, CARD7, NAC, CLR17.1, DEFCAP, VAMAS1
- Chromosome:
- 17p13
- Locus Type:
- gene with protein product
- Date approved:
- 2003-10-28
- Date modifiied:
- 2016-06-01
Related products to: NLRP1 Blocking Peptide
Related articles to: NLRP1 Blocking Peptide
- Pathogens, tissue damage, and cellular stress are detected by innate immune sensor molecules to drive inflammatory signaling and cell death. Mutations in the sensor NLRP1 are associated with inflammatory disease, but the regulation of this sensor is not well understood. Here, we find that LPS, a TLR4 ligand and canonical activator of innate immunity, inhibits NLRP1-mediated caspase activation, IL-18 release, and inflammatory cell death, PANoptosis. This inhibition requires TRIF but not MyD88, implicating TRIF-dependent TLR signaling. IRF3 is also required, suggesting an essential role for type I IFN signaling. Indeed, IFN-β production or treatment with exogenous IFN-α or IFN-β inhibits NLRP1-dependent PANoptosis in mouse bone marrow-derived macrophages and human macrophages and monocytes. Mechanistically, Nlrp1b/NLRP1 expression is significantly reduced in LPS- or type I IFN-treated cells. Overall, our study identifies a TLR4-TRIF-IRF3 signaling axis that induces type I IFNs to negatively regulate NLRP1 transcription, thereby blocking NLRP1-driven, caspase-1/caspase-8/RIPK3-dependent PANoptosis. These findings suggest type I IFNs as a potential therapeutic strategy for NLRP1-driven inflammatory diseases. - Source: PubMed
Publication date: 2026/07/29
Sharma Bhesh RajMummareddy HarisankeerthChadchan Sangappa BSarkar RomanEi Farran Chadi AKanneganti Thirumala-Devi - Yeast culture (YC) is widely applied as a functional feed additive, yet the mechanisms by which it regulates hepatic health, metabolism, and immune capacity in teleosts remain unclear. Here, juvenile were fed diets supplemented with 2.0% (YC2.0) or 8.0% YC (YC8.0) for 60 days, followed by hepatic histophysiological assessment, liver transcriptomic/metabolomic profiling, and an in vitro hepatocyte challenge with nervous necrosis virus (NNV). YC2.0 pincreased lipid droplet accumulation, improved antioxidant status, and lower aspartate aminotransferase(AST)/alanine aminotransferase (ALT)/alkaline phosphatase (ALP) and MDA in the liver than the control (Con) and YC8.0 groups. RNA-seq identified 915 hepatic differentially expressed genes (DEGs): YC2.0-specific genes were enriched in steroid hormone biosynthesis, bile secretion, and rhythmic regulation, whereas YC8.0-upregulated clusters were enriched in NOD-like receptor and JAK-STAT signaling, hematopoietic cell lineage, and apoptosis, with elevated immune- and apoptosis-related markers (, , , , and ). Metabolomics identified 680 differential metabolites across the three groups, showing that YC2.0 predominantly enhanced purine/nucleotide and glycerophospholipid metabolism, while YC8.0 shifted toward amino acid-centered pathways (arginine biosynthesis, histidine metabolism, and FoxO signaling). Multiomics integration revealed positive correlations of L-aspartic acid (L-Asp) and glutamic acid (Glu) with inflammatory DEGs, and of glycerophosphoethanolamine (Geptn) with apoptosis-related DEGs. In vitro, YC pretreatment alleviated NNV-induced cytopathic effects (CPEs) in hepatocytes, suppressed viral mRNA accumulation, and reduced the mRNA levels of inflammatory cytokines (β, , , , , and ) and immune pathway related DEGs. Collectively, these results characterize dose-dependent effects of YC on hepatic physiology and immune regulation, supporting its application as a functional aquafeed supplement. - Source: PubMed
Publication date: 2026/07/17
Yin ChenlinWang BoTang HaizhanZhang TongyaoZhai ZhongyiLi JiahangJin ChaofanBao ZhenminHu Jingjie - Bronchopulmonary dysplasia (BPD), a debilitating chronic respiratory condition afflicting preterm neonates, stems from oxidative injury and is characterized by arrested alveolar growth and aberrant inflammatory responses. This investigation uncovers a novel mechanistic axis in which the 20-hydroxyeicosatetraenoic acid (20-HETE)/GPR75 signaling cascade acts as a previously unrecognized driver of NLRP1 inflammasome activation in neonatal BPD, thereby linking oxidative stress to inflammatory signaling via p53. Using murine hyperoxia models, we observe that excessive oxygen exposure selectively upregulates GPR75 expression and 20-HETE biosynthesis within alveolar epithelial cells. Genetic inactivation of Gpr75 in vivo significantly attenuated hyperoxia-induced lung injury, oxidative stress, and NLRP1-dependent secretion of interleukin-1β and interleukin-18. Mechanistic dissection revealed that 20-HETE induces NLRP1 inflammasome assembly in rat alveolar epithelia via p53-mediated signaling. In vitro corroboration via lentiviral-mediated Gpr75 silencing, with scrambled shRNA serving as a negative control, further validated its role in hyperoxia-triggered NLRP1 activation and cytokine release (P < 0.01 vs. scrambled control). Collectively, these findings establish the 20-HETE/GPR75 axis as a critical regulator of inflammasome-dependent pathogenesis in BPD. Blockade of this axis inhibits inflammasome assembly and downstream inflammation by suppressing p53 signaling. These results highlight this axis as a promising therapeutic target to mitigate oxygen-induced injury and inflammatory sequelae in preterm infants. - Source: PubMed
Xu QiuXiangTian XiaoLiLi BinKang Jian - Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by profound cognitive decline, wherein chronic neuroinflammation plays a pivotal pathogenic role. Central to this inflammatory milieu is pyroptosis, a highly inflammatory form of programmed lytic cell death mediated by gasdermin proteins. This comprehensive review provides an in-depth synthesis of the cellular and molecular mechanisms underlying pyroptosis in AD. We detail the distinct roles of microglia as primary initiators responding to amyloid-beta (Aβ) and tau aggregates, alongside the specific vulnerabilities of neurons facing oxidative stress, astrocytes impacting metabolic support, and endothelial cells whose pyroptotic death contributes directly to blood-brain barrier disruption. At the molecular level, the priming and activation of the NLRP3 and NLRP1 inflammasomes by diverse triggers, including classical markers like Aβ, environmental neurotoxicants and metabolic stressors, converge on caspase-1 and caspase-8 activation. This cascade culminates in gasdermin D (GSDMD) and gasdermin E (GSDME) pore formation, leading to cellular lysis and the massive release of pro-inflammatory cytokines such as IL-1β and IL-18. Furthermore, this paper explores the emerging and critical concept of PANoptosis, highlighting the intricate crosstalk between pyroptosis, apoptosis, and necroptosis within PANoptosome complexes triggered by mitochondrial dysfunction. We evaluate current and prospective therapeutic strategies, ranging from multi-target natural and traditional herbal remedies to advanced nanomedicine, synthetic small molecules, and epigenetic gene therapies. By integrating insights from blood-based pyroptosis-associated molecular signatures and advanced targeted drug delivery systems, we emphasize the critical need for personalized, multi-targeted approaches to successfully harness pyroptosis modulation in the clinical management and treatment of AD. - Source: PubMed
Publication date: 2026/07/14
Hsu Chou-YiRaval Aditi DBainsal NeerajKaur IrwanjotBaig Mirza RTurakulov RustamSapaev IbrokhimHjazi AhmedAlghazali TawfeeqSmerat Aseel - Loss of function mutation in the human gene causes Hatipoglu syndrome leading to severe inflammasomopathy. A key feature of the disease is pancytopenia and patients require bone marrow transplantation, but the mechanism of cell loss is unclear since mutant mice have normal hematopoiesis, suggesting that a distinct mechanism of disease occurs in humans. Here, we present a model of human DPP9 deficiency leveraging reverse genetics in the MISTRG6 humanized mice. We found that CRISPR editing of human CD34 hematopoietic stem and progenitor cells (HSPCs) led to very efficient and persistent gene deletion in vivo. Human deletion recapitulated cytopenia in peripheral blood and in the bone marrow, and cell loss was cell intrinsic. However, deletion led to little transcriptional changes suggesting post-transcriptional regulation in human HSPCs. Mechanistically, DPP9 deficiency led to the activation of the CARD8 inflammasome resulting in HSPC pyroptosis, whereas NLRP1 was dispensable for cell death. Thus, our results reveal a unique human mechanism of disease and offer therapeutic insight for this inflammasomopathy. - Source: PubMed
Publication date: 2026/06/30
Xiao TianliBrewer J RichardCarlino MaximilianHan AilinTakabe YamatoLee Chia-YiZhang FengruiChen MiBlackburn Holly NicoleNassar Amin HWang QiankunBrennad KristenShan LiangSefik EsenKrause Diane SFlavell Richard A