Shank3 forms a complex with Gal-3 and ZBP-1 to alleviate PANoptosis in TIA of female ovariectomized mice DOI Creative Commons
Lei Zhang,

Yaowen Luo,

Jimeng Zhang

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Abstract Selective neuron death or loss, which induced by specific pathogen- and damage-associated molecular patterns (PAMPs DAMPs), was the main reason results in high morbidity, disability, mortality of transient ischemic attack (TIA) man postmenopausal women. Shank3, a key postsynaptic density, is correlated with synaptic dysfunction, oxidative stress, inflammatory, apoptosis poor outcomes stroke, although its role menopausal women TIA remains elusive. Here we discovered that Shank3 direct binds Gal-3, positive regulator aging inflammation, then regulates innate immune sensors ZBP-1, to drive inflammatory signaling cell death, PANoptosis, during TIA. Base on defeminization models (a stable female mouse OVX + model first established as well an vitro cultured primary desexualization tOGD/R model), blockade amplify stress arouse persistent behavioral deficits infarction formation, does not appear de-estrogen combination damage mice. We also observed Gal-3 ZBP-1 were members large multi-protein complex along Caspase 3, 7, 8, 9, 1, NLRP GSDMD, GSDME, RIPK 3 MLKL drove neuronal-special PANoptosis. In addition, administration natural inhibitor, D-allose, used for food sweetener, produces anti-PANoptosis effects via activating but inhibiting ZBP-1. Collectively, our findings establish previously unknown regulatory connection interaction among driver neuron-specific PANoptosis TIA, reveal activate such as, maybe potential strategy halt neuronal loss

Language: Английский

Implications of inflammatory cell death-PANoptosis in health and disease DOI
Hyun W. Bae,

Y.H. Jang,

Rajendra Karki

et al.

Archives of Pharmacal Research, Journal Year: 2024, Volume and Issue: 47(7), P. 617 - 631

Published: July 1, 2024

Language: Английский

Citations

5
ADAR1 protects pulmonary macrophages from sepsis-induced pyroptosis and lung injury through miR-21/A20 signaling DOI Creative Commons
Xiaojun Zhao, Jiangang Xie,

Chujun Duan

et al.

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 20(2), P. 464 - 485

Published: Dec. 5, 2023

Acute lung injury is a serious complication of sepsis with high morbidity and mortality. Pyroptosis proinflammatory form programmed cell death that leads to immune dysregulation organ dysfunction during sepsis. We previously found adenosine deaminase acting on double-stranded RNA 1 (ADAR1) plays regulatory roles in the pathology sepsis, but mechanism ADAR1 sepsis-induced pyroptosis remains unclear. Here, we mainly investigated effects underlying pulmonary macrophages through sequencing clinical samples, caecal ligation puncture (CLP)-induced septic mouse models, vitro cellular experiments using RAW264.7 cells lipopolysaccharide (LPS) stimulation. The results showed was activated peripheral blood mononuclear (PBMCs) from patients In CLP-induced model, macrophages. LPS-stimulated significantly increased activation NLRP3 inflammasome. downregulated PMBCs overexpression alleviated inflammasome activation. Mechanistically, macrophage were mediated by miR-21/A20/NLRP3 signalling cascade. attenuated hindered axis. Our study highlights role protecting against suggests targeting ADAR1/miR-21 as therapeutic opportunity sepsis-related injury.

Language: Английский

Citations

11
Z-nucleic acid sensor ZBP1 in sterile inflammation DOI
Qixiang Song,

Zehong Qi,

Kangkai Wang

et al.

Clinical Immunology, Journal Year: 2024, Volume and Issue: 261, P. 109938 - 109938

Published: Feb. 11, 2024

Language: Английский

Citations

4
PANoptosis in autoimmune diseases interplay between apoptosis, necrosis, and pyroptosis DOI Creative Commons

Kangnan Liu,

Mi Wang,

Dongdong Li

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 31, 2024

PANoptosis is a newly identified inflammatory programmed cell death (PCD) that involves the interplay of apoptosis, necrosis, and pyroptosis. However, its overall biological effects cannot be attributed to any one type PCD alone. regulated by signaling cascade triggered recognition pathogen-associated molecular patterns (PAMPs) damage-associated (DAMPs) various sensors. This triggers assembly PANoptosome, which integrates key components from other pathways via adapters ultimately activates downstream execution molecules, resulting in with necrotic, apoptotic, pyroptotic features. Autoimmune diseases are characterized reduced immune tolerance self-antigens, leading abnormal responses, often accompanied systemic chronic inflammation. Consequently, PANoptosis, as unique innate immune-inflammatory pathway, has significant pathophysiological relevance inflammation autoimmunity. most previous research on focused tumors infectious diseases, leaving activation role autoimmune unclear. review briefly outlines characteristics summarizes several PANoptosome complexes, their mechanisms, components. We also explored dual potential therapeutic approaches targeting PANoptosis. Additionally, we existing evidence for explore regulatory mechanisms involved.

Language: Английский

Citations

4
Shank3 forms a complex with Gal-3 and ZBP-1 to alleviate PANoptosis in TIA of female ovariectomized mice DOI Creative Commons
Lei Zhang,

Yaowen Luo,

Jimeng Zhang

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Abstract Selective neuron death or loss, which induced by specific pathogen- and damage-associated molecular patterns (PAMPs DAMPs), was the main reason results in high morbidity, disability, mortality of transient ischemic attack (TIA) man postmenopausal women. Shank3, a key postsynaptic density, is correlated with synaptic dysfunction, oxidative stress, inflammatory, apoptosis poor outcomes stroke, although its role menopausal women TIA remains elusive. Here we discovered that Shank3 direct binds Gal-3, positive regulator aging inflammation, then regulates innate immune sensors ZBP-1, to drive inflammatory signaling cell death, PANoptosis, during TIA. Base on defeminization models (a stable female mouse OVX + model first established as well an vitro cultured primary desexualization tOGD/R model), blockade amplify stress arouse persistent behavioral deficits infarction formation, does not appear de-estrogen combination damage mice. We also observed Gal-3 ZBP-1 were members large multi-protein complex along Caspase 3, 7, 8, 9, 1, NLRP GSDMD, GSDME, RIPK 3 MLKL drove neuronal-special PANoptosis. In addition, administration natural inhibitor, D-allose, used for food sweetener, produces anti-PANoptosis effects via activating but inhibiting ZBP-1. Collectively, our findings establish previously unknown regulatory connection interaction among driver neuron-specific PANoptosis TIA, reveal activate such as, maybe potential strategy halt neuronal loss

Language: Английский

Citations

0