Posttranslational modifications of NLRP3 and their regulatory roles in inflammasome activation DOI Open Access
Ying Qin, Wei Zhao

European Journal of Immunology, Journal Year: 2023, Volume and Issue: 53(10)

Published: June 29, 2023

Abstract The NACHT, LRR, and PYD domains‐containing protein 3 (NLRP3) inflammasome is a multimolecular complex that plays fundamental role in inflammation. Optimal activation of NLRP3 crucial for host defense against pathogens the maintenance immune homeostasis. Aberrant activity has been implicated various inflammatory diseases. Posttranslational modifications (PTMs) NLRP3, key sensor, play critical roles directing controlling severity inflammation diseases, such as arthritis, peritonitis, bowel disease, atherosclerosis, Parkinson's disease. Various PTMs, including phosphorylation, ubiquitination, SUMOylation, could direct control by affecting stability, ATPase activity, subcellular localization, oligomerization well association between other components. Here, we provide an overview PTMs their summarize potential anti‐inflammatory drugs targeting PTMs.

Language: Английский

Drugging the NLRP3 inflammasome: from signalling mechanisms to therapeutic targets DOI

Lieselotte Vande Walle,

Mohamed Lamkanfi

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 23(1), P. 43 - 66

Published: Nov. 29, 2023

Language: Английский

Citations

111
Inducing trained immunity in pro-metastatic macrophages to control tumor metastasis DOI
Chuanlin Ding, Rejeena Shrestha, Xiaojuan Zhu

et al.

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(2), P. 239 - 254

Published: Jan. 5, 2023

Language: Английский

Citations

96
NLRP3 inflammasome signalling in Alzheimer's disease DOI Creative Commons
Róisín M. McManus, Eicke Latz

Neuropharmacology, Journal Year: 2024, Volume and Issue: 252, P. 109941 - 109941

Published: March 31, 2024

Every year, 10 million people develop dementia, the most common of which is Alzheimer's disease (AD). To date, there no way to prevent cognitive decline and therapies are limited. This review provides a neuroimmunological perspective on progression AD, discusses immune-targeted that in preclinical clinical trials may impact development this disease. Specifically, we look role NLRP3 inflammasome, its triggers brain how activation can contribute dementia. We summarise range inhibitors targeting inflammasome downstream pathways under investigation, discuss future therapeutic perspectives for devastating condition.

Language: Английский

Citations

27
The role of NLRP3 inflammasome in type 2 inflammation related diseases DOI Creative Commons

Xu Shenming,

Dan Wang, Lina Tan

et al.

Autoimmunity, Journal Year: 2024, Volume and Issue: 57(1)

Published: Feb. 8, 2024

Type 2 inflammation related diseases, such as atopic dermatitis, asthma, and allergic rhinitis, are diverse affect multiple systems in the human body. It is common for individuals to have co-existing type which can impose a significant financial living burden on patients. However, exact pathogenesis of these diseases still unclear. The NLRP3 inflammasome protein complex composed protein, ASC, Caspase-1, activated through various mechanisms, including NF-κB pathway, ion channels, lysosomal damage. plays role immune response pathogens cellular Recent studies indicated strong correlation between abnormal activation onset inflammation. Additionally, it has been demonstrated that suppressing expression effectively diminishes inflammatory response, highlighting its promising therapeutic applications. Therefore, this article reviews development therapy diseases.

Language: Английский

Citations

24
The Role of Oxidative Stress in Tumorigenesis and Progression DOI Creative Commons
Kexin Li,

Zhangyuzi Deng,

Chunran Lei

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 441 - 441

Published: March 2, 2024

Oxidative stress refers to the imbalance between production of reactive oxygen species (ROS) and endogenous antioxidant defense system. Its involvement in cell senescence, apoptosis, series diseases has been demonstrated. Advances carcinogenic research have revealed oxidative as a pivotal pathophysiological pathway tumorigenesis be involved lung cancer, glioma, hepatocellular carcinoma, leukemia, so on. This review combs effects on each phase fate determination, three features are discussed. takes part processes ranging from tumor death via pathways like mitochondrial stress, endoplasmic reticulum ferroptosis. It can affect by engaging complex relationships death, cancer. The influence progression is multi-stage interlaced process that includes two aspects promotion inhibition, with mitochondria core regulation. A deeper more comprehensive understanding conducive exploring therapies.

Language: Английский

Citations

21
Emerging Roles of Macrophage Polarization in Osteoarthritis: Mechanisms and Therapeutic Strategies DOI Creative Commons
Z. L. Yuan,

Jiang De-cheng,

Mengzhu Yang

et al.

Orthopaedic Surgery, Journal Year: 2024, Volume and Issue: 16(3), P. 532 - 550

Published: Jan. 31, 2024

Osteoarthritis (OA) is the most common chronic degenerative joint disease in middle‐aged and elderly people, characterized by pain dysfunction. Macrophages are key players OA pathology, their activation state has been studied extensively. Various studies have suggested that macrophages might respond to stimuli microenvironment changing phenotypes pro‐inflammatory or anti‐inflammatory phenotypes, which called macrophage polarization. accumulate become polarized (M1 M2) many tissues, such as synovium, adipose tissue, bone marrow, mesenchymal tissues joints, while resident well other stromal cells, including fibroblasts, chondrocytes, osteoblasts, form function an integrated unit. In this study, we focus exclusively on synovial macrophages, tissue osteoclasts, investigate roles development of OA. We review recent findings related polarization OA, pathogenesis, molecular pathways, therapeutics. summarize several signaling pathways reprogramming NF‐κB, MAPK, TGF‐β, JAK/STAT, PI3K/Akt/mTOR, NLRP3. Of note, despite increasing availability treatments for osteoarthritis, like intra‐articular injections, surgery, cellular therapy, demand more effective clinical therapies remained steady. Therefore, also describe current prospective therapeutic methods deem be a target, physical stimulus, chemical compounds, biological molecules, enhance cartilage repair alleviate progression

Language: Английский

Citations

20
The Immunopathogenesis of a Cytokine Storm: The Key Mechanisms Underlying Severe COVID-19 DOI Creative Commons

Luka Hiti,

Tijana Markovič,

Mitja Lainščak

et al.

Cytokine & Growth Factor Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

A cytokine storm is marked by excessive pro-inflammatory release, and has emerged as a key factor in severe COVID-19 cases - making it critical therapeutic target. However, its pathophysiology was poorly understood, which hindered effective treatment. SARS-CoV-2 initially disrupts angiotensin signalling, promoting inflammation through ACE-2 downregulation. Some patients' immune systems then fail to shift from innate adaptive immunity, suppressing interferon responses leading pyroptosis neutrophil activation. This amplifies tissue damage inflammation, creating loop. The result the disruption of Th1/Th2 Th17/Treg balances, lymphocyte exhaustion, extensive blood clotting. Cytokine treatments include glucocorticoids suppress system, monoclonal antibodies neutralize specific cytokines, JAK inhibitors block receptor signalling. most treatment options for mitigating infection remain vaccines preventive measure antiviral drugs early stages infection. article synthesizes insights into dysregulation COVID-19, offering framework better understand storms improve monitoring, biomarker discovery, strategies other conditions involving storms.

Language: Английский

Citations

6
MAP Kinase Signaling at the Crossroads of Inflammasome Activation DOI

Alex Vervaeke,

Mohamed Lamkanfi

Immunological Reviews, Journal Year: 2025, Volume and Issue: 329(1)

Published: Jan. 1, 2025

ABSTRACT Inflammasomes are crucial mediators of both antimicrobial host defense and inflammatory pathology, requiring stringent regulation at multiple levels. This review explores the pivotal role mitogen‐activated protein kinase (MAPK) signaling in modulating inflammasome activation through various regulatory mechanisms. We detail recent advances understanding MAPK‐mediated NLRP3 priming, licensing activation, with emphasis on MAPK‐induced activator protein‐1 (AP‐1) ERK1 JNK licensing, TAK1 connecting death receptor to activation. Furthermore, we discuss novel insights into MAPK human NLRP1 focusing MAP3K member ZAKα as a key linking ribosomal stress Lastly, work elucidating how Bacillus anthracis lethal toxin (LeTx) manipulates induce macrophage apoptosis an immune evasion strategy, counteraction this effect genotype‐specific Nlrp1b certain rodent strains.

Language: Английский

Citations

2
Neuroinflammation and immunometabolism in neurodegenerative diseases DOI

Neha Lonkar,

Eicke Latz, Róisín M. McManus

et al.

Current Opinion in Neurology, Journal Year: 2025, Volume and Issue: 38(2), P. 163 - 171

Published: Feb. 12, 2025

Immunometabolism is an emerging field of research investigating the ability immune cells to modulate their metabolic activity for optimal function. While this has been extensively examined in peripheral like macrophages, only recently have these studies extended assess immunometabolic microglia, innate brain. Microglia are highly metabolically flexible and can utilize different nutrients diverse functions. Like other cells, they undergo reprogramming on stimulation inflammatory, neurodegenerative conditions such as Alzheimer's disease (AD). In recent years, researchers looked at intricate mechanisms that microglial uncovered key links between altered metabolism, neuroinflammation, involvement disease-associated risk genes. This review highlights significantly contributed our understanding dysregulation observed activated microglia AD, unveiling novel targets therapeutic intervention.

Language: Английский

Citations

2
The Role of the NLRP3 Inflammasome and Programmed Cell Death in Acute Liver Injury DOI Open Access
Chaoqun Yu, Peng Chen, Longyu Miao

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3067 - 3067

Published: Feb. 4, 2023

Acute liver injury (ALI) is a globally important public health issue that, when severe, rapidly progresses to acute failure, seriously compromising the life safety of patients. The pathogenesis ALI defined by massive cell death in liver, which triggers cascade immune responses. Studies have shown that aberrant activation nod-like receptor protein 3 (NLRP3) inflammasome plays an role various types and NLRP3 causes programmed (PCD), these effectors can turn regulate activation. This indicates inextricably linked PCD. In this review, we summarize PCD (APAP, ischemia reperfusion, CCl4, alcohol, Con A, LPS/D-GalN induced ALI) analyze underlying mechanisms provide references for future relevant studies.

Language: Английский

Citations

39