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The NLRP3 inflammasome is a potential mechanism and therapeutic target for perioperative neurocognitive disorders.

Perioperative neurocognitive disorders (PNDs) are frequent complications associated with cognitive impairment during the perioperative perio … nonical pathway induced by nucleotide oligomerization domain (NOD)-, leucine-rich repeat (LRR)- and pyrin domain-containing protein 3 (NLRP3) inflammasomes contributes to PNDs, which suggests that targeting NLRP3 inflammasomes may be an effective strategy for the treatment of PNDs. Therefore, inhibiting upstream activators and blocking the assembly of the NLRP …

Alloferon-1 ameliorates estrogen deficiency-induced osteoporosis through dampening the NLRP3/caspase-1/IL-1β/IL-18 signaling pathway.

Alloferon-1 is an insect polypeptide that has anti-inflammatory, antitumor and antiviral activity. This study aimed to determine the effects … he vertebrae bone tissues, including nucleotide-binding oligomerization domain-like-receptor family pyrin domain-containing 3 (NLRP3), cysteinyl aspartate specific proteinase-1 (Caspase-1), interleukin 1β (IL-1β) and interleukin 18 (IL-18) which were determined by immunofluorescence staining and western blot. Overall, the present study provides evidence for th …

CARD-only proteins regulate in vivo inflammasome responses and ameliorate gout.

Inflammatory responses are crucial for controlling infections and initiating tissue repair. However, excessive and uncontrolled inflammation causes inflammatory disease. Processing and release of the pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18 depend on caspase-1 activation within inflammasomes. Assembly of inflammasomes is initiated upon activation of cytosolic pattern recognition receptors (PRRs), followed by sequential polymerization of pyrin domain (PYD)-containing and caspase recruitment domain (CARD)-containing proteins mediated by homotypic PYD and CARD interactions. Sma…

Inflammasome activation and assembly in Huntington's disease.

Huntington's disease (HD) is a rare neurodegenerative disease characterized by motor, cognitive, and psychiatric symptoms. Inflammasomes are multiprotein complexes capable of sensing pathogen-associated and damage-associated molecular patterns, triggering innate immune pathways. Activation of inflammasomes results in a pro-inflammatory cascade involving, among other molecules, caspases and interleukins. NLRP3 (nucleotide-binding domain, leucine-rich-repeat containing family, pyrin domain-containing 3) is the most studied inflammasome complex, and its activation results in caspase-1 mediated cl…

Resveratrol protects human bronchial epithelial cells against nickel-induced toxicity via suppressing p38 MAPK, NF-κB signaling, and NLRP3 inflammasome activation.

Nickel is a common environmental pollutant that can impair the lung, but the underlying mechanisms have not yet been fully elucidated. Furthermore, natural products are generally used to inhibit cell damage induced by heavy metal. Resveratrol possesses wide biological activities, including anti-inflammation and antioxidative stress. This study was conducted to explore the toxicity of nickel on human bronchial epithelial (BEAS-2B) cells and evaluate the protective effect of resveratrol. The results showed that nickel could induce cell apoptosis, increase oxidative stress, and promote the expres

GDF11 inhibits cardiomyocyte pyroptosis and exerts cardioprotection in acute myocardial infarction mice by upregulation of transcription factor HOXA3.

NLRP3 (Nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3) inflammasome-mediated cardiomyocytes pyroptosis plays a crucial part in progression of acute myocardial infarction (MI). GDF11 (Growth Differentiation Factor 11) has been reported to generate cytoprotective effects in phylogenesis and multiple diseases, but the mechanism that GDF11 contributes to cardioprotection of MI and cardiomyocytes pyroptosis remains poorly understood. In our study, we first determined that GDF11 was abnormally downregulated in the heart tissue of MI mice and hypoxic cardiomyocytes.…

Роль NLRP3 испарения в нейродегенеративных и метаболических заболеваниях и в соответствующих перспективных терапевтических вмешательствах.

Инфламасомы представляют собой внутриклеточные мультипротеиновые комплексы в цитоплазме, которые регулируют воспаление во врожденной иммунной системе в ответ на патогены и на прием самопроизводственных молекул. Последние достижения значительно улучшили наше понимание активации нуклеотидно-обязательного олигомеризации домена-подобный рецептору (NLR) семейный пирин, содержащий 3 (NLRP3) воспаление на молекулярном уровне. NLRP3 принадлежит подсемейству NLRP, которая активирует Caspase 1, что приводит к производству провоспалительных цитокинов (interleukin) 1β и интерлейкин 18) и пироптоз. Это вос

Совпадение в аннотации оригинала
Inflammasomes are intracellular multiprotein complexes in the cytoplasm that regulate inflammation activation in the innate immune system in response to pathogens and to host self-derived molecules. Recent advances greatly improved our understanding of the activation of nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain contain…

PPARG activation by pioglitazone promotes mitophagy and inhibits the NLRP3 inflammasome to alleviate arthritic joint inflammation and bone damage.

Rheumatoidarthritis (RA) is an autoimmune disease accompanied by joint swelling,stiffness, and pain, leading to a sharp decline in quality o … drial DNA; mtROS: mitochondrial reactive oxygen species; NAC: N-acetylcysteine; NLRP1B: NLR family, pyrin domain containing 1B; NLRP3: NLR family, pyrin domain containing 3; NLRC4: NLR family, CARD domain containing 4; OGTT: oral glucose tolerance test; PBS: phosphate-buffered saline; PINK1: PTEN induced putative kinase 1; PIOG: pioglitazone; PPARG/PPARγ: pero …

Crystal Structure of NLRP3 NACHT Domain With an Inhibitor Defines Mechanism of Inflammasome Inhibition.

The NLRP3 inflammasome assembles in response to a variety of pathogenic and sterile danger signals, resulting in the production of interleukin-1β and interleukin-18. NLRP3 is a key component of the innate immune system and has been implicated as a driver of a number of acute and chronic diseases. We report the 2.8 Å crystal structure of the NLRP3 NACHT domain in complex with an inhibitor. The structure defines a binding pocket formed by the four subdomains of the NACHT domain, and shows the inhibitor acts as an intramolecular glue, which locks the protein in an inactive conformation. It provid

Vaccines targeting the inflammasome protein ASC reduce inflammation and downstream pathology in multiple disease models.

The inflammasome is an innate immune complex responsible for aberrant interleukin-1β (IL-1β) signaling in numerous chronic inflammatory dise … activation and neutrophil responses. Three vaccines targeting different regions of the ASC protein (pyrin domain, linker region, and the caspase activation and recruitment domain) successfully targeted ASC, reduced IL-1β, and reduced neutrophil activation. Combining these three vaccines into one cocktail vaccine yielded similar efficacy in the gout model with …

TIM3 alleviates microglia-mediated neuroinflammation in neuropathic pain by negatively regulating glycolysis-driven NLRP3 inflammasome activation.

Microglia-mediated neuroinflammation has emerged as a potential therapeutic target for neuropathic pain. T-cell immunoglobulin domain and mu … itivity. Mechanistically, TIM3 negatively regulates glycolysis, thereby suppressing NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation and preventing further microglia-driven inflammatory responses in vivo and in vitro. Furthermore, both glycolysis and the glycolysis-associated NLRP3 inflammasome are essential for TIM3-mediated n …

USP22 suppresses the NLRP3 inflammasome by degrading NLRP3 via ATG5-dependent autophagy.

The NLRP3 inflammasome is involved in a diverse range of inflammatory diseases. The activation of inflammasomes must be tightly regulated to … in 1 beta; LPS: lipopolysaccharide; NLRC4: NLR family, CARD domain containing 4; NLRP3: NLR family, pyrin domain containing 3; PYCARD/ASC: PYD and CARD domain containing; TNF/TNF-α: tumor necrosis factor; USP22: ubiquitin specific peptidase 22.

Targeting NLRP3 Inflammasomes in Myocarditis: Potential Therapeutic Strategies and Clinical Translation.

Myocarditis can be caused by viral infections, systematic autoimmune diseases, and as a reaction to prescribed medications, and the nucleotide-binding domain leucine-rich repeat pyrin domain-containing 3 (NLRP3) inflammasome is implicated in its pathophysiology. Here, we explore pharmaceutical and other therapies that modulate NLRP3 activation and may therefore be useful for treating myocarditis. Pharmaceutical agents such as colchicine, SGLT2 inhibitors (empagliflozin and canagliflozin), calpain inhibitors, and sacubitril/valsartan have shown promise in reducing inflammation and preserving ca…

Targeting the NLRP3 inflammasome in Parkinson's disease: From molecular mechanism to therapeutic strategy.

Parkinson's disease is the second most common neurodegenerative disease, characterized by substantial loss of dopaminergic (DA) neurons, the formation of Lewy bodies (LBs) in the substantia nigra, and pronounced neuroinflammation. The nucleotide-binding domain like leucine-rich repeat- and pyrin domain-containing protein 3 (NLRP3) inflammasome is one of the pattern recognition receptors (PRRs) that function as intracellular sensors in response to both pathogenic microbes and sterile triggers associated with Parkinson's disease. These triggers include reactive oxygen species (ROS), misfolding p…

The Role of Methyl Canthin-6-one-2-carboxylate in Targeting the NLRP3 Inflammasome in Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent synovial inflammation, joint destruction, and systemic complications. The nucleotide-binding domain, leucine-rich repeat family, pyrin domain-containing-3 (NLRP3) inflammasome plays a pivotal role in RA pathogenesis by driving the release of pro-inflammatory cytokines and exacerbating oxidative stress. Recent studies identified methyl canthin-6-one-2-carboxylate (Cant) as a potential therapeutic agent that modulates the NLRP3 inflammasome pathway. This review explores the mechanistic role of Cant in RA treat…

Targeting Pyroptotic Cell Death Pathways in Retinal Disease.

Pyroptosis is a gasdermin-mediated, pro-inflammatory form of cell death distinct from apoptosis. In recent years, increasing attention has s … he most in retinal cells are the nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, caspase-1, and gasdermin D (GSDMD). Targeting these proteins may help us develop new drug therapies, or supplement existing therapies, in the treatment of retinal diseases. As novel mechanisms of pyroptosis come to …

Parkin Prevents Glutamate Excitotoxicity Through Inhibiting NLRP3 Inflammasome in Retinal Ganglion Cells.

Glutamate excitotoxicity is one of the important pathophysiological culprits in retinal ganglion cells (RGCs) damage after acute optic nerve … ctive effects on RGCs by inhibiting nucleotide-binding domain leucine-rich repeat containing family pyrin domain containing 3 (NLRP3) inflammasome. Moreover, the genetic and pharmacological downregulation of NLRP3 improved survival of RGCs against glutamate excitotoxicity. In the end, knockdown of Parkin exacerbated glutamate induced RGCs damage via triggering …

Expression of genes encoding inflammasome sensor subunits in the duodenal and colonic mucosae of dogs with chronic enteropathy.

Inflammasomes play a pivotal role in gastrointestinal homeostasis and inflammation. However, it remains elusive whether the nucleotide-binding oligomerization domain-like receptor (NLR) family inflammasomes, such as NLR family pyrin domain-containing (NLRP) 3, NLRP6, and NLRP12, are involved in the pathogenesis of canine chronic enteropathy (CE), which includes antibiotic-responsive enteropathy (ARE), food-responsive enteropathy (FRE), immunosuppressant-responsive enteropathy (IRE), and non-responsive enteropathy (NRE). Thus, we measured mRNA expression of NLRP3, NLRP6, and NLRP12 in the intes…

Licochalcone B specifically inhibits the NLRP3 inflammasome by disrupting NEK7-NLRP3 interaction.

The activation of the nucleotide oligomerization domain (NOD)-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome is related to the pathogenesis of a wide range of inflammatory diseases, but drugs targeting the NLRP3 inflammasome are still scarce. In the present study, we demonstrated that Licochalcone B (LicoB), a main component of the traditional medicinal herb licorice, is a specific inhibitor of the NLRP3 inflammasome. LicoB inhibits the activation of the NLRP3 inflammasome in macrophages but has no effect on the activation of AIM2 or NLRC4 inflammasome. Mech…

Dual therapeutic targeting of intra-articular inflammation and intracellular bacteria enhances chondroprotection in septic arthritis.

Bacterial infections involving joints and vital organs represent a challenging clinical problem because of the two concurrent therapeutic go … mation by targeting the NLRP3 (nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3) inflammasome protects articular cartilage from damage in a murine model of knee septic arthritis. Together, concurrent mitigation of intra-articular inflammation and local adjuvant targeting of intracellular bacteria represents a promi …