The role of inflammasomes in human diseases and their potential as therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Jan. 5, 2024

Abstract Inflammasomes are large protein complexes that play a major role in sensing inflammatory signals and triggering the innate immune response. Each inflammasome complex has three components: an upstream sensor molecule is connected to downstream effector such as caspase-1 through adapter ASC. Inflammasome formation typically occurs response infectious agents or cellular damage. The active then triggers activation, followed by secretion of pro-inflammatory cytokines pyroptotic cell death. Aberrant activation activity contribute development diabetes, cancer, several cardiovascular neurodegenerative disorders. As result, recent research increasingly focused on investigating mechanisms regulate assembly well potential targeting inflammasomes treat various diseases. Multiple clinical trials currently underway evaluate therapeutic distinct inflammasome-targeting therapies. Therefore, understanding how different disease pathology may have significant implications for developing novel strategies. In this article, we provide summary biological pathological roles health disease. We also highlight key evidence suggests could be strategy new disease-modifying therapies effective conditions.

Language: Английский

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Gingerenone A Attenuates Ulcerative Colitis via Targeting IL‐17RA to Inhibit Inflammation and Restore Intestinal Barrier Function

Advanced Science, Journal Year: 2024, Volume and Issue: 11(28)

Published: April 19, 2024

Abstract Ulcerative colitis (UC) is a complicated and recurrent intestinal disease. Currently available drugs for UC treatment are scarce, therefore, novel therapeutic the urgently to be developed. Gingerenone A (GA) phenolic compound known its anti‐inflammatory effect, but effect on remains unknown. Here, it shown that GA protects mice against UC, which closely associated with inhibiting mucosal inflammation enhancing barrier integrity in vivo vitro. Of note, RNA sequencing analysis demonstrates an evident correlation IL‐17 signaling pathway after treatment, this further corroborated by Western blot. Mechanistically, directly interacts IL‐17RA protein through pull‐down, surface plasmon resonance molecular dynamics simulation. Importantly, lentivirus‐mediated IL‐17RA/Act1 knock‐down or co‐treatment brodalumab/ixekizumab significantly impairs protective effects of DSS‐induced dysfunction, suggesting critical role GA‐mediated protection UC. Overall, these results indicate effective agent mainly direct binding inhibit inflammatory activation.

Language: Английский

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Britannin as a novel NLRP3 inhibitor, suppresses inflammasome activation in macrophages and alleviates NLRP3-related diseases in mice

Acta Pharmacologica Sinica, Journal Year: 2024, Volume and Issue: 45(4), P. 803 - 814

Published: Jan. 3, 2024

Language: Английский

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Therapeutic potential and pharmacological mechanisms of Traditional Chinese Medicine in gout treatment

Acta Pharmacologica Sinica, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Language: Английский

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Advances in the roles of ATF4 in osteoporosis

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 169, P. 115864 - 115864

Published: Nov. 9, 2023

Osteoporosis (OP) is characterized by reduced bone mass, decreased strength, and enhanced fragility fracture risk. Activating transcription factor 4 (ATF4) plays a role in cell differentiation, proliferation, apoptosis, redox balance, amino acid uptake, glycolipid metabolism. ATF4 induces the differentiation of marrow mesenchymal stem cells (BM-MSCs) into osteoblasts, increases osteoblast activity, inhibits osteoclast formation, promoting formation remodeling. In addition, mediates energy metabolism osteoblasts promotes angiogenesis. also involved mediation adipogenesis. can selectively accumulate osteoblasts. directly interact with RUNT-related 2 (RUNX2) up-regulate expression osteocalcin (OCN) osterix (Osx). Several upstream factors, such as Wnt/β-catenin BMP2/Smad signaling pathways, have been ATF4-mediated differentiation. osteoclastogenesis mediating receptor activator nuclear κ-B (NF-κB) ligand (RANKL) signaling. agents, parathyroid (PTH), melatonin, natural compounds, reported to regulate mediate this review, we comprehensively discuss biological activities maintaining homeostasis inhibiting OP development. has become therapeutic target for treatment.

Language: Английский

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Tabersonine, a natural NLRP3 inhibitor, suppresses inflammasome activation in macrophages and attenuate NLRP3-driven diseases in mice

Acta Pharmacologica Sinica, Journal Year: 2023, Volume and Issue: 44(6), P. 1252 - 1261

Published: Jan. 10, 2023

Language: Английский

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Asiaticoside exerts neuroprotection through targeting NLRP3 inflammasome activation

Phytomedicine, Journal Year: 2024, Volume and Issue: 127, P. 155494 - 155494

Published: Feb. 28, 2024

Language: Английский

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Small molecule α-methylene-γ-butyrolactone, an evolutionarily conserved moiety in sesquiterpene lactones, ameliorates arthritic phenotype via interference DNA binding activity of NF-κB

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(8), P. 3561 - 3575

Published: April 8, 2024

Rheumatoid arthritis (RA) is an inflammatory disease accompanied by abnormal synovial microenvironment (SM). Sesquiterpene lactones (SLs) are the main anti-inflammatory ingredients of many traditional herbs utilized in RA treatment.

Language: Английский

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Heme oxygenase 1-mediated ferroptosis in Kupffer cells initiates liver injury during heat stroke

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(9), P. 3983 - 4000

Published: May 13, 2024

With the escalating prevalence of global heat waves, stroke has become a prominent health concern, leading to substantial liver damage. Unlike other forms injury, stroke-induced damage is characterized by cytotoxicity and heightened inflammation, directly contributing elevated mortality rates. While clinical assessments have identified bilirubin levels as indicative Kupffer cell dysfunction, their specific correlation with injury remains unclear. Our hypothesis proposes involvement ferroptosis during stroke, initiating IL-1

Language: Английский

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Exploring the health benefits of food bioactive compounds from a perspective of NLRP3 inflammasome activation: an insight review

Critical Reviews in Food Science and Nutrition, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 26

Published: Jan. 6, 2025

The food industry has been focusing on bioactive compounds with multiple physiological and immunological properties that benefit human health. These compounds, including polyphenols, flavonoids, terpenoids, have great potential to limit inflammatory responses especially NLRP3 inflammasome activation, which is a key innate immune platform for inflammation. Current studies revealed numerous promising activities unraveling metabolic disorders excessive by directly indirectly regulating the activation. This review explores hazards, microbial abiotic factors, may trigger NLRP3-mediated illnesses It also highlights in can suppress activation through various mechanisms, linking its inhibition different pathways. Especially, this provided further insight into NLRP3-related targets where interact block process, as well mechanisms how these facilitate inactivation processes.

Language: Английский

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