PANoptosis: Novel insight into regulated cell death and its potential role in cardiovascular diseases (Review) DOI Creative Commons
Xinyu Gao,

Cuixue Ma,

Shan Liang

et al.

International Journal of Molecular Medicine, Journal Year: 2024, Volume and Issue: 54(3)

Published: July 4, 2024

PANoptosis, a complex form of proinflammatory programmed cell death, including apoptosis, pyroptosis and necroptosis, has been an emerging concept in recent years that widely reported cancer, infectious diseases neurological disorders. Cardiovascular (CVDs) are important global health problem, posing serious threat to individuals' lives. An increasing body research shows inflammation pivotal role CVDs, which provides theoretical basis for PANoptosis promote the progression CVDs. To date, only sporadic studies on CVDs have its field not fully explored. Elucidating various modes cardiomyocyte specific molecular mechanisms links among death under stressful stimuli is notable clinical significance deeper understanding pathophysiology The present review summarizes pyroptosis, necroptosis their prospects

Language: Английский

Therapeutic potential of PANoptosis: innate sensors, inflammasomes, and RIPKs in PANoptosomes DOI Creative Commons
Ankit Pandeya, Thirumala‐Devi Kanneganti

Trends in Molecular Medicine, Journal Year: 2023, Volume and Issue: 30(1), P. 74 - 88

Published: Nov. 15, 2023

The innate immune system initiates cell death pathways in response to pathogens and cellular stress. Cell can be either non-lytic (apoptosis) or lytic (PANoptosis, pyroptosis, necroptosis). PANoptosis has been identified as an inflammatory, pathway driven by caspases RIPKs that is regulated PANoptosome complexes, making it distinct from other pathways. Several complexes (including ZBP1-, AIM2-, RIPK1-, NLRP12-PANoptosomes) have characterized date. Furthermore, implicated infectious inflammatory diseases, cancers, homeostatic perturbations. Therefore, targeting its molecular components offers significant potential for therapeutic development. This review covers PANoptosomes their assembly, PANoptosome-mediated mechanisms, ongoing progress developing therapeutics target PANoptosis.

Language: Английский

Citations

80
PANoptosis: Mechanisms, biology, and role in disease DOI Open Access

Xu Sun,

Yanpeng Yang,

Xiaona Meng

et al.

Immunological Reviews, Journal Year: 2023, Volume and Issue: 321(1), P. 246 - 262

Published: Oct. 12, 2023

Summary Cell death can be executed through distinct subroutines. PANoptosis is a unique inflammatory cell modality involving the interactions between pyroptosis, apoptosis, and necroptosis, which mediated by multifaceted PANoptosome complexes assembled via integrating components from other modalities. There growing interest in process function of PANoptosis. Accumulating evidence suggests that occurs under diverse stimuli, for example, viral or bacterial infection, cytokine storm, cancer. Given impact across disease spectrum, this review briefly describes relationships highlights key molecules formation activation, outlines roles diseases together with potential therapeutic targeting. We also discuss important concepts pressing issues future research. Improved understanding its mechanisms crucial identifying novel targets strategies.

Language: Английский

Citations

71
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

61
Fn-OMV potentiates ZBP1-mediated PANoptosis triggered by oncolytic HSV-1 to fuel antitumor immunity DOI Creative Commons
Shuo Wang,

An Song,

Jun Xie

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 30, 2024

Oncolytic viruses (OVs) show promise as a cancer treatment by selectively replicating in tumor cells and promoting antitumor immunity. However, the current immunogenicity induced OVs for is relatively weak, necessitating thorough investigation of mechanisms underlying its induction Here, we that HSV-1-based (oHSVs) trigger ZBP1-mediated PANoptosis (a unique innate immune inflammatory cell death modality), resulting augmented effects. Mechanistically, oHSV enhances expression interferon-stimulated genes, leading to accumulation endogenous Z-RNA subsequent activation ZBP1. To further enhance potential oHSV, conduct screening identify Fusobacterium nucleatum outer membrane vesicle (Fn-OMV) can increase execution proteins. The combination Fn-OMV demonstrates potent immunogenicity. Taken together, our study provides deeper understanding oHSV-induced immunity, promising strategy combines with Fn-OMV.

Language: Английский

Citations

20
Gasdermin E dictates inflammatory responses by controlling the mode of neutrophil death DOI Creative Commons
Fengxia Ma, Laxman Ghimire, Qian Ren

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 9, 2024

Abstract Both lytic and apoptotic cell death remove senescent damaged cells in living organisms. However, they elicit contrasting pro- anti-inflammatory responses, respectively. The precise cellular mechanism that governs the choice between these two modes of remains incompletely understood. Here we identify Gasdermin E (GSDME) as a master switch for neutrophil pyroptotic death. tightly regulated GSDME cleavage activation aging neutrophils are mediated by proteinase-3 caspase-3, leading to pyroptosis. deficiency does not alter overall survival rate; instead, it specifically precludes pyroptosis skews towards apoptosis, thereby attenuating inflammatory responses due augmented efferocytosis macrophages. In clinically relevant acid-aspiration-induced lung injury model, neutrophil-specific deletion reduces pulmonary inflammation, facilitates inflammation resolution, alleviates injury. Thus, controlling mode death, dictates host outcomes, providing potential therapeutic target infectious diseases.

Language: Английский

Citations

16
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
Current evidence and therapeutic implication of PANoptosis in cancer DOI Creative Commons
Dickson Kofi Wiredu Ocansey, Fei Qian,

Peipei Cai

et al.

Theranostics, Journal Year: 2023, Volume and Issue: 14(2), P. 640 - 661

Published: Dec. 26, 2023

Regulated cell death (RCD) is considered a critical pathway in cancer therapy, contributing to eliminating cells and influencing treatment outcomes. The application of RCD marked by its potential targeted therapy immunotherapy. As type RCD, PANoptosis has emerged as unique form programmed (PCD) characterized features pyroptosis, apoptosis, necroptosis but cannot be fully explained any these pathways alone. It regulated multi-protein complex called the PANoptosome. relatively new concept first described 2019, been shown play role many diseases, including cancer, infection, inflammation. This study reviews PCD particularly emergence implication developing therapeutic strategies for cancer. Studies have that characterization patterns can predict survival response immunotherapy chemotherapy, highlighting used target treatment. also plays limiting spread cells. allows elimination multiple address various challenges treatment, drug resistance immune evasion. Moreover, active investigation mechanisms agents induce likely yield effective treatments improve patient Research on still ongoing, it rapidly evolving field with lead

Language: Английский

Citations

33
PANoptosis-based molecular subtyping and HPAN-index predicts therapeutic response and survival in hepatocellular carcinoma DOI Creative Commons
Fei Song, Chenggui Wang,

Jiazhen Mao

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: June 15, 2023

Hepatocellular carcinoma (HCC) is a highly prevalent and fatal cancer. The role of PANoptosis, novel form programmed cell death, in HCC yet to be fully understood. This study focuses on identifying analyzing PANoptosis-associated differentially expressed genes (HPAN_DEGs), aiming enhance our understanding pathogenesis potential treatment strategies.We analyzed from TCGA IGCG databases mapped them the PANoptosis gene set, 69 HPAN_DEGs. These underwent enrichment analyses, consensus clustering analysis was used determine three distinct subgroups based their expression profiles. immune characteristics mutation landscape these were evaluated, drug sensitivity predicted using HPAN-index relevant databases.The HPAN_DEGs mainly enriched pathways associated with cycle, DNA damage, Drug metabolism, Cytokines, Immune receptors. We identified subtypes (Cluster_1, SFN+PDK4-; Cluster_2, SFN-PDK4+; Cluster_3, SFN/PDK4 intermediate expression) profiles exhibited clinical outcomes, characteristics, landscapes. HPAN-index, generated by machine learning levels HPAN_DEGs, as an independent prognostic factor for HCC. Moreover, high group response immunotherapy, while low showed small molecule targeted drugs. Notably, we observed that YWHAB plays significant Sorafenib resistance.This crucial tumor growth, infiltration, resistance Additionally, discovered constructed predict immunotherapeutic sensitivity. Our findings underscore resistance, presenting valuable insights personalized therapeutic strategy development

Language: Английский

Citations

28
A comparative study of apoptosis, pyroptosis, necroptosis, and PANoptosis components in mouse and human cells DOI Creative Commons
Sk Mohiuddin Choudhury, Roman Sarkar, Rajendra Karki

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(2), P. e0299577 - e0299577

Published: Feb. 27, 2024

Regulated cell death is a key component of the innate immune response, which provides first line defense against infection and homeostatic perturbations. However, can also drive pathogenesis. The most well-defined pathways be categorized as nonlytic (apoptosis) lytic (pyroptosis, necroptosis, PANoptosis). While specific triggers are known to induce each these pathways, it unclear whether all types express proteins required activate pathways. Here, we assessed protein expression compared responses non-immune cells human mouse origin canonical pyroptotic (LPS plus ATP), apoptotic (staurosporine), necroptotic (TNF-α z-VAD), PANoptotic (influenza A virus infection) stimuli. When fibroblasts, both cells, macrophages, expressed higher levels activated effectors more robustly, including caspase-1, gasdermins, caspase-8, RIPKs, in response Our findings highlight importance considering type when examining mechanisms regulating inflammation death. Improved understanding that contain machinery execute different forms their link critical identify new strategies target cellular populations for treatment infectious diseases, inflammatory disorders, cancer.

Language: Английский

Citations

15
Regulated cell death‐amplified sonodynamic anti‐tumor immune nanotherapeutics DOI Creative Commons
Liqiang Zhou, Yangmengfan Chen, Dong Xie

et al.

BMEMat, Journal Year: 2024, Volume and Issue: unknown

Published: March 4, 2024

Abstract Nanomedicine‐assisted sonodynamic therapy (SDT) has emerged as one of the most promising cancer therapies due to its unique advantages high penetration, non‐radiation, and excellent oxidative stress effect, but always suffered from self‐protection mechanism apoptosis resistance characteristics evolutionarily mutated cells. Regulated cell death (RCD) received increasing attention in precision treatments because significant role synergistically sensitizing reversing immunosuppressive microenvironment during SDT nanomedicine‐triggered immunogenic death. Herein, paradigmatic research RCD‐augmented tumor immunotherapeutics are typically introduced, such autophagy blockade, ferroptosis targeting, pyroptosis induction, necroptosis initiation, cuproptosis actuation, PANoptosis trigger, coordinated anti‐tumor mechanisms discussed detail. Multiple analysis focusing on currently unsolved problems future development prospects RCD‐based nano‐oncology medicine also prospected further strengthen expand scope therapeutic applications.

Language: Английский

Citations

15