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The crosstalk of neutrophil extracellular trap-inflammasome and their roles in disease progression.

Neutrophil extracellular traps (NETs) are a network of fibrous structures composed of DNA, histones, and antimicrobial proteins released by … e response. This review elaborates on the constituent proteins and molecular regulation of NETs and inflammasomes, summarizes the crosstalk between NETs and inflammasomes and its negative effects in the disease process, and also discusses the therapeutic effects of drugs targeting NETs and/or inflammasomes on related diseases.

Targeting the NLRP3 inflammasome in sepsis: Molecular mechanisms and therapeutic strategies.

Sepsis is a life-threatening organ dysfunction triggered by a dysregulated host response to infection, with immune homeostasis imbalance at the core of its pathological mechanism. The NACHT, leucin-rich repeat (LRR) and pyrin domain (PYD)-containing protein 3 (NLRP3) inflammasome, as an innate immune sensor, plays a critical role in the development and progression of sepsis. Upon activation, the NLRP3 inflammasome triggers caspase-1 activation, which mediates the maturation and release of IL-1β and IL-18, as well as pyroptosis. Studies have demonstrated that inhibiting NLRP3 inflammasome activ

The NOX2-ROS-NLRP3 inflammasome axis in traumatic brain injury.

BACKGROUND: Phagocyte NADPH oxidase 2 (NOX2) is an enzyme complex responsible for reactive oxygen species (ROS) production. Chronic NOX2 activity sustains oxidative stress/damage and drives neuroinflammation following traumatic brain injury (TBI). NOX2 acts as a priming signal for NLRP3 inflammasome activation, which also plays a role in secondary injury after TBI. GSK2795039 is a small molecule brain penetrable drug that inhibits NOX2 in a NADPH competitive manner. Here, we investigated whether pharmacological inhibition of NOX2 using GSK2795039 can reduce secondary neuroinflammation after TB

Neuroprotective activity of thiolutin in epileptic mice: the inhibition of NLRP3 inflammasome.

Neuroinflammation is a key mechanism in epileptogenesis. Thiolutin (THL), an inhibitor of NACHT, LRR, and PYD domains-containing protein 3 ( … s, and improved cognitive dysfunction in epileptic mice, accompanied by reduced activation of NLRP3 inflammasomes in hippocampal neurons and microglia. These findings suggest that THL exerts neuroprotective effects by blocking NLRP3 inflammasome activation, thereby mitigating neuroinflammatory responses, neuronal injury, and cognitive dysfunction in epileptic m …

Identification of a novel Songorine derivative as a potent NLRP3 inflammasome inhibitor.

As a key intracellular pattern-recognition receptor, NLRP3 senses diverse pathogen- and damage-associated molecular patterns (PAMPs and DAMPs), initiating inflammasome assembly and pyroptotic cell death. Aberrant NLRP3 activation contributes to various chronic inflammatory diseases, including atherosclerosis, Alzheimer's disease, and rheumatoid arthritis, underscoring its therapeutic relevance. In this study, we designed and synthesized compound 8a, a structurally optimized derivative of the diterpenoid alkaloid songorine. In lipopolysaccharide (LPS)- and nigericin-stimulated macrophage models

Inflammasome and ventricular arrhythmogenesis: Pathogenic interplay and potential targets on the horizon.

Life-threatening ventricular arrhythmias (VAs) pose a significant challenge in clinical management due to their impact on mortality, particularly the risk of sudden cardiac death, which remains a concern despite the use of only partially effective anti-arrhythmic drugs and repeated catheterablation. There is also a need for more precise risk stratification tools for implantable cardioverter defibrillators (ICD). Sustained ventricular tachycardia (VT) most commonly occurs in patients with a history of myocardial infarction (MI) or non ischemic cardiomyopathy characterized by fibrotic ventricula

Shikonin inhibits NLRP3 inflammasome activation and controls inflammatory disease.

Shikonin (SHK) is a plant-derived naphthoquinone known for its anti-inflammatory activity, though the mechanism remains largely unexplored. The NLRP3 inflammasome, one of the most studied inflammasomes, can cause uncontrolled inflammation and drive various diseases when dysregulated. Here, we confirmed that SHK specifically abolished NLRP3 inflammasome activation by suppressing caspase-1 maturation and the secretion of IL-1β and IL-18. Our data demonstrated that SHK disrupted NLRP3 inflammasome assembly, primarily by blocking NLRP3 and ASC binding, thereby preventing ASC oligomerization and AS…

Human cytomegalovirus protein US18 promotes NLRP3 inflammasome activation.

Human cytomegalovirus (HCMV) infection of monocytes results in inflammatory response by triggering the activation of inflammasomes and subsequent release of inflammatory cytokines including IL-1β and IL-18 and pyroptosis. However, the mechanisms by which HCMV induces inflammatory response remain unclear. Here, we identified that the HCMV protein US18 promotes NLRP3 inflammasome activation, IL-1β release and pyroptosis. US18 associates with the NLRP3 inflammasome components NEK7, NLRP3 and pro-IL-1β, and promotes the oligomerization and speck formation of NLRP3. Knockdown of US18 inhibits HCMV-…

Ось микробиота-инфламасомного мозга в качестве патогенного посредника нейродегенеративных расстройств.

В различных нейродегенеративных расстройствах важную роль играет воспаление и связанная с этим воспаленная активация. Наиболее распространенными и обширными исследованиями воспаления являются NLRP3 воспаления, которые возникают из-за патогенов или опасных сигналов, содействующих провокационной реакции. Внеклеточный СПС также активирует NLRP3 путем стимулирования purinergic рецептора P2X7 (P2X7R). Было установлено, что центральные и периферийные клетки, в том числе клетки в кишечнике, активировали воспаление во время патологических изменений в сочетании с воспалением в различных нейродегенерати

Совпадение в аннотации оригинала
In various neurodegenerative disorders, inflammation and associated inflammasome activation play an important role. The most prevalent and extensively researched inflammasomes are NLRP3 inflammasomes, which are triggered by pathogens or danger signals mediating inflammatory reaction. Extracellular ATP also activates NLRP3 by stimulating the purinergic recept…

Роль NLRP3 инфламасома в множестве склероза: патогенез и фармакологическое применение.

Множественный склероз (MS) широко признается в качестве хронического провокационного аутоиммунного расстройства, характеризующегося демиэлизацией центральной нервной системы (КНС) и нейродегенерацией. Гиперактивация иммунной и подстрекательской реакции признается в качестве ключевого фактора, способствующего патогенезу и прогрессированию MS. Среди различных иммунных и подстрекательских реакций исследователи все больше концентрируют внимание на воспалении — комплексе белков. Запуск и активация воспламенения неразрывно связаны с началом НР. В частности, NLRP3 воспаляет, наиболее широко изучавший

Palmitoleate protects against lipopolysaccharide-induced inflammation and inflammasome activity.

Inflammation is part of natural immune defense mechanism against any form of infection or injury. However, prolonged inflammation could perturb cell homeostasis and contribute to the development of metabolic and inflammatory diseases, including maternal obesity, diabetes, cardiovascular diseases, and metabolic dysfunction-associated steatotic liver diseases (MASLD). Polyunsaturated fatty acids have been shown to mitigate inflammatory response by generating specialized proresolving lipid mediators, which take part in resolution of inflammation. Similarly here, we show that palmitoleate, an omeg

Cadmium activates the innate immune system through the AIM2 inflammasome.

Cadmium (Cd) is a widely used heavy metal and has recently been recognized as a possible source of human toxicity due to its ability to accumulate in organs. Accumulation of heavy metals has several adverse effects, including inducing inflammation, in multiple organs, such as the testis. However, how Cd ions are sensed by host cells and how tissue inflammation eventually occurs remains unclear. Here, we show that Cd activates the AIM2 inflammasome by mediating genomic DNA release into the cytoplasm after DNA damage via oxidative stress, to trigger IL-1β secretion and pyroptosis. Specifically,

Breaking the barriers: Overcoming cancer resistance by targeting the NLRP3 inflammasome.

Inflammation has a pivotal role in the initiation and progression of various cancers, contributing to crucial processes such as metastasis, angiogenesis, cell proliferation and invasion. Moreover, the release of cytokines mediated by inflammation within the tumour microenvironment (TME) has a crucial role in orchestrating these events. The activation of inflammatory caspases, facilitated by the recruitment of caspase-1, is initiated by the activation of pattern recognition receptors on the immune cell membrane. This activation results in the production of proinflammatory cytokines, including I

Asiaticoside exerts neuroprotection through targeting NLRP3 inflammasome activation.

BACKGROUND: Parkinson's disease (PD), a neurodegenerative disorder, is characterized by motor symptoms due to the progressive loss of dopaminergic neurons in the substantia nigra (SN) and striatum (STR), alongside neuroinflammation. Asiaticoside (AS), a primary active component with anti-inflammatory and neuroprotective properties, is derived from Centella asiatica. However, the precise mechanisms through which AS influences PD associated with inflammation are not yet fully understood. PURPOSE: This study aimed to explore the protective mechanism of AS in PD. METHODS: Targets associated with

The CARD8 inflammasome dictates HIV/SIV pathogenesis and disease progression.

While CD4+ T cell depletion is key to disease progression in people living with HIV and SIV-infected macaques, the mechanisms underlying this depletion remain incompletely understood, with most cell death involving uninfected cells. In contrast, SIV infection of "natural" hosts such as sooty mangabeys does not cause CD4+ depletion and AIDS despite high-level viremia. Here, we report that the CARD8 inflammasome is activated immediately after HIV entry by the viral protease encapsulated in incoming virions. Sensing of HIV protease activity by CARD8 leads to rapid pyroptosis of quiescent cells wi

Blockage of the NLRP3 inflammasome by MCC950 inhibits migration and invasion in adenomyosis.

RESEARCH QUESTION: Does the NOD-like receptor protein 3 (NLRP3) inflammasome have an effect in adenomyosis? DESIGN: Fresh-frozen endometrial tissues and paraffin specimens were obtained from endometrial tissues from patients with adenomyosis and controls. Western blot, quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were applied to assess expression of the NLRP3 inflammasome components. Primary eutopic endometrial stromal cells were isolated from the uteri of patients with adenomyosis. After NLRP3 was knocked down using small interfering RNA, prolifer

Roles of the Caspase-11 Non-Canonical Inflammasome in Rheumatic Diseases.

Inflammasomes are intracellular multiprotein complexes that activate inflammatory signaling pathways. Inflammasomes comprise two major classes: canonical inflammasomes, which were discovered first and are activated in response to a variety of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs), and non-canonical inflammasomes, which were discovered recently and are only activated in response to intracellular lipopolysaccharide (LPS). Although a larger number of studies have successfully demonstrated that canonical inflammasomes, particularly the NLRP…

Molecular regulation of NLRP3 inflammasome activation during parasitic infection.

Parasitic diseases are a serious global health concern, causing many common and severe infections, including Chagas disease, leishmaniasis, and schistosomiasis. The NLRP3 inflammasome belongs to the NLR (nucleotide-binding domain leucine-rich-repeat-containing proteins) family, which are cytosolic proteins playing key roles in the detection of pathogens. NLRP3 inflammasomes are activated in immune responses to Plasmodium, Leishmania, Toxoplasma gondii, Entamoeba histolytica, Trypanosoma cruzi, and other parasites. The role of NLRP3 is not fully understood, but it is a crucial component of the …

Toxoplasma gondii infection associated with inflammasome activation and neuronal injury.

Toxoplasma gondii (TOXO) infection typically results in chronic latency due to its ability to form cysts in the brain and other organs. Latent toxoplasmosis could promote innate immune responses and impact brain function. A large body of evidence has linked TOXO infection to severe mental illness (SMI). We hypothesized that TOXO immunoglobulin G (IgG) seropositivity, reflecting previous infection and current latency, is associated with increased circulating neuron-specific enolase (NSE), a marker of brain damage, and interleukin-18 (IL-18), an innate immune marker, mainly in SMI. We included 7

Роль Microglial Mayhem NLRP3 Inflammasome в мультиклерозовой патологии.

ВВЕДЕНИЕ: В настоящем обзоре рассматривается сложная взаимосвязь между NLR inflammasomes, в частности NLRP3, воспалением, и иммунной нейродегенеративной болезнью, множественным склерозом (MS). Хотя точная этиология MS по-прежнему остается труднодостижимой, убедительные исследования подчеркивают ключевую роль иммунной реакции в прогрессии заболеваний. В частности, проведенные в последнее время исследования свидетельствуют о значительном участии НЛП3 в различных аутоиммунных болезнях, что способствует углубленному изучению их воздействия на РС.МЕТОД: В обзоре основное внимание уделяется разъясне…