Role of NLRP3 in Parkinson's disease: Specific activation especially in dopaminergic neurons DOI Creative Commons

Juan Yu,

Zhanghong Zhao,

Yuanyuan Li

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(7), P. e28838 - e28838

Published: March 28, 2024

Parkinson's disease (PD) is a neurodegenerative disorder with motor symptoms like bradykinesia, tremors, and balance issues. The pathology recognized by progressively degenerative nigrostriatal dopaminergic neurons (DANs) loss. Its exact pathogenesis unclear. Numerous studies have shown that nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) contributes to the of PD. Previous demonstrated over-activation NLRP3 inflammasome in microglia indirectly leads loss DANs, which can worsen In recent years, autopsy analyses PD patients models revealed upregulation expression within DANs activation sufficient drive neuronal loss, whereas microglial occurs after death, inhibition intraneuronal prevents degeneration DANs. this review, we provide research evidence related as well focus on possible mechanisms neurons, aiming new way thinking about prevention

Language: Английский

The NLR family of innate immune and cell death sensors DOI Creative Commons
Balamurugan Sundaram, Rebecca E. Tweedell, Sivakumar Prasanth Kumar

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(4), P. 674 - 699

Published: April 1, 2024

Nucleotide-binding oligomerization domain (NOD)-like receptors, also known as nucleotide-binding leucine-rich repeat receptors (NLRs), are a family of cytosolic pattern recognition that detect wide variety pathogenic and sterile triggers. Activation specific NLRs initiates pro- or anti-inflammatory signaling cascades the formation inflammasomes—multi-protein complexes induce caspase-1 activation to drive inflammatory cytokine maturation lytic cell death, pyroptosis. Certain inflammasomes act integral components larger death complexes—PANoptosomes—driving another form PANoptosis. Here, we review current understanding evolution, structure, function in health disease. We discuss concept NLR networks their roles driving immunity. An improved mechanistic may provide therapeutic strategies applicable across infectious diseases cancer.

Language: Английский

Citations

69
Pyroptosis in health and disease: mechanisms, regulation and clinical perspective DOI Creative Commons
Yifan Liu,

Renjie Pan,

Yuzhen Ouyang

et al.

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

Published: Sept. 20, 2024

Language: Английский

Citations

44
Inflammasome components as new therapeutic targets in inflammatory disease DOI
Rebecca C. Coll, Kate Schroder

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 9, 2024

Language: Английский

Citations

30
Inflammation and resolution in obesity DOI
Matúš Soták, Madison Clark, Bianca E Suur

et al.

Nature Reviews Endocrinology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 24, 2024

Language: Английский

Citations

23
Urolithin A alleviates NLRP3 inflammasome activation and pyroptosis by promoting microglial mitophagy following spinal cord injury DOI

Kongbin Chen,

Jiahao Ying,

Jian Zhu

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 148, P. 114057 - 114057

Published: Jan. 18, 2025

Language: Английский

Citations

3
Mitochondrial DNA leakage: underlying mechanisms and therapeutic implications in neurological disorders DOI Creative Commons
Guangming Zhang,

Huayuan Wei,

Anliu Zhao

et al.

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Feb. 7, 2025

Mitochondrial dysfunction is a pivotal instigator of neuroinflammation, with mitochondrial DNA (mtDNA) leakage as critical intermediary. This review delineates the intricate pathways leading to mtDNA release, which include membrane permeabilization, vesicular trafficking, disruption homeostatic regulation, and abnormalities in dynamics. The escaped activates cytosolic sensors, especially cyclic gmp-amp synthase (cGAS) signalling inflammasome, initiating neuroinflammatory cascades via pathways, exacerbating spectrum neurological pathologies. therapeutic promise targeting discussed detail, underscoring necessity for multifaceted strategy that encompasses preservation homeostasis, prevention leakage, reestablishment dynamics, inhibition activation sensors. Advancing our understanding complex interplay between neuroinflammation imperative developing precision interventions disorders.

Language: Английский

Citations

3
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
Gut microbiota: a novel target for exercise-mediated regulation of NLRP3 inflammasome activation DOI Creative Commons
Jun Chen,

Shaohui Jia,

Xiaoguang Xue

et al.

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 6, 2025

The NOD-like receptor family pyrin domain-containing 3 (NLRP3) is a key pattern recognition in the innate immune system. Its overactivation leads to production of pro-inflammatory cytokines, such as IL-1β and IL-18, which contribute development progression various diseases. In recent years, evidence has shown that gut microbiota plays an important role regulating activation NLRP3 inflammasome. Variations function composition can directly or indirectly influence inflammasome by influencing bacterial components metabolites. Additionally, exercise been effectively reduce while promoting beneficial changes microbiota. This suggests may play mediating effects on regulation. review explores impact activation, examines mechanisms through mediates anti-inflammatory exercise, providing new avenues for research.

Language: Английский

Citations

2
Inhibition of macrophage polarization and pyroptosis in collagen-induced arthritis through MSC-exo and ginsenoside Rh2 DOI Creative Commons

Zhongsheng Zhou,

Shuhui Wu,

Yang Li

et al.

Arthritis Research & Therapy, Journal Year: 2025, Volume and Issue: 27(1)

Published: Jan. 9, 2025

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, tissue damage, and fibrosis, significantly affecting the quality of life. While there are currently some effective treatments available, they often come with side effects. There an urgent need to find new that can further improve therapeutic outcomes reduce Our study investigates role Mesenchymal Stem Cell exosomes (MSC-exo) combined Ginsenoside Rh2 (Rh2) in treatment RA. We specifically focus on how this strategy influences macrophage polarization pyroptosis. This research utilized collagen-induced rat model. The findings reveal combination MSC-exo inhibit M1 macrophages, increase proportion M2-like suppress M1-like pyroptosis via NLRP3/Caspase11/GSDMD-N pathway. In model, showed synergistic contributes deeper understanding RA's pathogenesis presents potential targeted interventions. application offers promising insights for future innovative strategies RA treatment, paving way more management disease.

Language: Английский

Citations

2
Stem cell-derived extracellular vesicles in the therapeutic intervention of Alzheimer's Disease, Parkinson's Disease, and stroke DOI Creative Commons

W. Zhou,

Xudong Wang,

Yumeng Dong

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(8), P. 3358 - 3384

Published: Jan. 1, 2024

With the increase in aging population, occurrence of neurological disorders is rising.Recently, stem cell therapy has garnered attention due to its convenient sourcing, minimal invasiveness, and capacity for directed differentiation.However, there are some disadvantages, such as poor quality control, safety assessments, ethical logistical issues.Consequently, scientists have started shift their from cells extracellular vesicles similar structures properties.Beyond these parallels, can enhance biocompatibility, facilitate easy traversal barriers, minimize side effects.Furthermore, cell-derived be engineered load drugs modify surfaces treatment outcomes.In this review, we summarize functions native vesicles, subsequently review strategies engineering applications Alzheimer's disease, Parkinson's stroke, discuss challenges solutions associated with clinical translation vesicles.

Language: Английский

Citations

12