Inflammation in obesity, diabetes, and related disorders

Immunity, Год журнала: 2022, Номер 55(1), С. 31 - 55

Опубликована: Янв. 1, 2022

Язык: Английский

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Structural Mechanisms of NLRP3 Inflammasome Assembly and Activation

Annual Review of Immunology, Год журнала: 2023, Номер 41(1), С. 301 - 316

Опубликована: Фев. 8, 2023

As an important sensor in the innate immune system, NLRP3 detects exogenous pathogenic invasions and endogenous cellular damage responds by forming inflammasome, a supramolecular complex that activates caspase-1. The three major components of inflammasome are NLRP3, which captures danger signals recruits downstream molecules; caspase-1, elicits maturation cytokines IL-1β IL-18 processing gasdermin D to mediate cytokine release pyroptosis; ASC (apoptosis-associated speck-like protein containing caspase recruitment domain), functions as bridge connecting In this article, we review structural information has been obtained on its or subcomplexes, with special focus inactive cage, active NLRP3-NEK7 (NIMA-related kinase 7)-ASC disk, PYD-PYD CARD-CARD homotypic filamentous scaffolds inflammasome. We further implicate structure-derived mechanisms for assembly activation

Язык: Английский

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The role of the NLRP3 inflammasome and pyroptosis in cardiovascular diseases

Nature Reviews Cardiology, Год журнала: 2023, Номер 21(4), С. 219 - 237

Опубликована: Ноя. 3, 2023

Язык: Английский

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Hyperuricemia and its related diseases: mechanisms and advances in therapy

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Авг. 28, 2024

Abstract Hyperuricemia, characterized by elevated levels of serum uric acid (SUA), is linked to a spectrum commodities such as gout, cardiovascular diseases, renal disorders, metabolic syndrome, and diabetes, etc. Significantly impairing the quality life for those affected, prevalence hyperuricemia an upward trend globally, especially in most developed countries. UA possesses multifaceted role, antioxidant, pro-oxidative, pro-inflammatory, nitric oxide modulating, anti-aging, immune effects, which are significant both physiological pathological contexts. The equilibrium circulating urate hinges on interplay between production excretion, delicate balance orchestrated transporter functions across various epithelial tissues cell types. While existing research has identified involvement numerous biological processes signaling pathways, precise mechanisms connecting disease etiology remain be fully elucidated. In addition, influence genetic susceptibilities environmental determinants calls detailed nuanced examination. This review compiles data from global epidemiological studies clinical practices, exploring foundations transporters depth. Furthermore, we uncover complex induced inflammation influences individuals with association its relative disease, offering foundation innovative therapeutic approaches advanced pharmacological strategies.

Язык: Английский

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The role of inflammasomes in vascular cognitive impairment

Molecular Neurodegeneration, Год журнала: 2022, Номер 17(1)

Опубликована: Янв. 9, 2022

There is an increasing prevalence of Vascular Cognitive Impairment (VCI) worldwide, and several studies have suggested that Chronic Cerebral Hypoperfusion (CCH) plays a critical role in disease onset progression. However, there limited understanding the underlying pathophysiology VCI, especially relation to CCH. Neuroinflammation significant contributor progression VCI as increased systemic levels proinflammatory cytokine interleukin-1β (IL-1β) has been extensively reported patients. Recently it established CCH can activate inflammasome signaling pathways, involving NLRP3 AIM2 inflammasomes critically regulate IL-1β production. Given neuroinflammation early event important we understand its molecular cellular mechanisms enable development disease-modifying treatments reduce structural brain damage cognitive deficits are observed clinically elderly. Hence, this review aims provide comprehensive insight into involved pathogenesis CCH-induced VCI.

Язык: Английский

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TREM-1 governs NLRP3 inflammasome activation of macrophages by firing up glycolysis in acute lung injury

International Journal of Biological Sciences, Год журнала: 2022, Номер 19(1), С. 242 - 257

Опубликована: Ноя. 23, 2022

The triggering receptor expressed on myeloid cells-1 (TREM-1) is a pro-inflammatory immune potentiating acute lung injury (ALI).However, the mechanism of TREM-1-triggered inflammation response remains poorly understood.Here, we showed that TREM-1 blocking attenuated NOD-, LRRand pyrin domain-containing 3 (NLRP3) inflammasome activation and glycolysis in LPS-induced ALI mice.Then, observed enhanced glucose consumption, induced glycolysis, inhibited oxidative phosphorylation macrophages.Specifically, inhibition with 2-deoxyglucose diminished NLRP3 macrophages triggered by TREM-1.Hypoxia-inducible factor-1α (HIF-1α) critical transcriptional regulator glycolysis.We further found facilitated HIF-1α accumulation translocation to nucleus via phosphoinositide 3-kinase (PI3K)/AKT/mammalian target rapamycin (mTOR) pathway.Inhibiting mTOR or also suppressed TREM-1-induced metabolic reprogramming NLRP3/caspase-1 activation.Overall, mTOR/HIF-1α/glycolysis pathway novel underlying TREM-1-governed activation.Therapeutic targeting TREM-1-activated could be beneficial for treating preventing inflammatory diseases, such as ALI.

Язык: Английский

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SIRT1 pathway in Parkinson’s disease: a faraway snapshot but so close

Inflammopharmacology, Год журнала: 2022, Номер 31(1), С. 37 - 56

Опубликована: Дек. 29, 2022

Abstract Silent information regulator (SIRT) has distinctive enzymatic activities and physiological functions to control cell-cycle progression, gene expression, DNA stability by targeting histone non-histone proteins. SIRT1 enhances synaptic formation activity, therefore, can reduce the progression of various degenerative brain diseases including Parkinson’s disease (PD). activity is decreased aging with a subsequent increased risk for development diseases. Inhibition promotes inflammatory reactions since inhibits transcription nuclear factor kappa B (NF-κB) which also activation via microRNA miR-34a NAD synthesis. highly expressed in microglia as well neurons, antioxidant anti-inflammatory effects. Therefore, this review aimed find possible role PD neuropathology. neuroprotective effects; downregulation during p53 expression may increase vulnerability neuronal cell deaths. neuropathology linked sequence changes release pro-inflammatory cytokines due signaling pathways. In addition, oxidative stress, disorders, mitochondrial dysfunction, apoptosis contribute mutually Thus, activators play crucial mitigation through amelioration apoptosis,

Язык: Английский

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Targeting phenylpyruvate restrains excessive NLRP3 inflammasome activation and pathological inflammation in diabetic wound healing

Cell Reports Medicine, Год журнала: 2023, Номер 4(8), С. 101129 - 101129

Опубликована: Июль 21, 2023

Moderate inflammation is essential for standard wound healing. In pathological conditions, such as diabetes, protracted and refractory wounds are associated with excessive inflammation, manifested by persistent proinflammatory macrophage states. However, the mechanisms still unclear. Herein, we perform a metabolomic profile find significant phenylpyruvate accumulation in diabetic foot ulcers. Increased impairs healing augments inflammatory responses, whereas reducing via dietary phenylalanine restriction relieves uncontrolled benefits wounds. Mechanistically, ingested into macrophages scavenger receptor CD36-dependent manner, binds to PPT1, inhibits depalmitoylase activity, thus increasing palmitoylation of NLRP3 protein. found enhance protein stability, decrease lysosome degradation, promote inflammasome activation release factors, interleukin (IL)-1β, finally triggering phenotype. Our study suggests potential strategy targeting prevent

Язык: Английский

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Inhibitors of the NLRP3 inflammasome pathway as promising therapeutic candidates for inflammatory diseases (Review)

International Journal of Molecular Medicine, Год журнала: 2023, Номер 51(4)

Опубликована: Март 21, 2023

The inflammasome regulates innate immunity by serving as a signaling platform. Nod‑like receptor protein 3 (NLRP3) inflammasome, equipped with NLRP3, the adaptor apoptosis‑associated speck‑like (ASC) and pro‑caspase‑1, is far most extensively studied well‑characterized inflammasome. A variety of stimuli can activate NLRP3 When activated, recruits ASC activates resulting in inflammatory cytokine maturation secretion, which associated inflammation pyroptosis. However, aberrant activation has been linked to various diseases, including atherosclerosis, ischemic stroke, Alzheimer's disease, diabetes mellitus bowel disease. Therefore, emerged promising therapeutic target for diseases. In present review, systematic searches were performed using 'NLRP3 inhibitor(s)' 'inflammatory disease(s)' key words. By browsing literature from 2012 2022, 100 articles retrieved, 35 excluded they reviews, editorials, retracted or unavailable online, 65 included. According retrieved literature, current understanding pathway diseases was summarize, inhibitors targeting other components products highlighted. Additionally, review briefly discusses novel efforts clinical research.

Язык: Английский

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The role of dopamine in NLRP3 inflammasome inhibition: Implications for neurodegenerative diseases

Ageing Research Reviews, Год журнала: 2023, Номер 87, С. 101907 - 101907

Опубликована: Март 8, 2023

Язык: Английский

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