Life Sciences, Journal Year: 2024, Volume and Issue: unknown, P. 123241 - 123241
Published: Nov. 1, 2024
Language: Английский
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
European Journal of Immunology, Journal Year: 2023, Volume and Issue: 53(11)
Published: Feb. 13, 2023
Regulated cell death (RCD) triggered by innate immune activation is an important strategy for host survival during pathogen invasion and perturbations of cellular homeostasis. There are two main categories RCD, including nonlytic lytic pathways. Apoptosis the most well-characterized inflammatory pyroptosis necroptosis pathways among best known forms. While these were historically viewed as independent RCD pathways, extensive evidence cross-talk their molecular components created a knowledge gap in our mechanistic understanding pathway components, which led to identification PANoptosis. PANoptosis unique that regulated PANoptosome complexes upon sensing pathogens, pathogen-associated patterns (PAMPs), damage-associated (DAMPs) or cytokines produced downstream. Cytosolic sensors regulators, such ZBP1, AIM2 RIPK1, promote assembly PANoptosomes drive In this review, we discuss highlight mechanisms assembly, regulation identified date. We also how mutations linked diseases. Given impact specifically, across disease spectrum, improved will be critical identifying new therapeutic targets strategies.
Language: Английский
Citations
74
Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(8), P. 1632 - 1643
Published: Aug. 23, 2023
Pyroptosis, apoptosis, necroptosis, and ferroptosis, which are the most well-studied regulated cell death (RCD) pathways, contribute to clearance of infected or potentially neoplastic cells, highlighting their importance in homeostasis, host defense against pathogens, cancer, a wide range other pathologies. Although these four RCD pathways employ distinct molecular cellular processes, emerging genetic biochemical studies have suggested remarkable flexibility crosstalk among them. The pyroptosis, apoptosis necroptosis is more evident responses infection, has led conceptualization PANoptosis. In this review, we provide brief overview mechanisms ferroptosis maintaining homeostasis. We discuss intricate current evidence supporting PANoptosis, focusing on infectious diseases cancer. Understanding fundamental processes various crucial inform development new therapeutics many diseases, including sterile inflammation,
Language: Английский
Citations
48
Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(12)
Published: Dec. 21, 2023
Abstract Pyroptosis, apoptosis, and necroptosis are mainly programmed cell death (PCD) pathways for host defense homeostasis. PANoptosis is a newly distinct inflammatory PCD pathway that uniquely regulated by multifaceted PANoptosome complexes highlights significant crosstalk coordination among pyroptosis (P), apoptosis (A), and/or necroptosis(N). Although some studies have focused on the possible role of PANpoptosis in diseases, pathogenesis complex underestimated. Furthermore, progress related agonists or inhibitors disorders has not yet been thoroughly discussed. In this perspective, we provide perspectives context diverse pathological conditions human diseases. The treatment targeting also summarized. conclusion, involved plenty including but limited to microbial infections, cancers, acute lung injury/acute respiratory distress syndrome (ALI/ARDS), ischemia-reperfusion, organic failure. seems be double-edged sword conditions, as induces negative impact prognosis like COVID-19 ALI/ARDS, while provides protection from HSV1 Francisella novicida infection, kills cancer cells suppresses tumor growth colorectal cancer, adrenocortical carcinoma, other cancers. Compounds endogenous molecules promising therapeutic strategies, which can act PANoptosomes-associated members regulate PANoptosis. More researches needed better understand pathology develop treatment.
Language: Английский
Citations
43
Cancer Gene Therapy, Journal Year: 2024, Volume and Issue: 31(7), P. 970 - 983
Published: March 29, 2024
Abstract This comprehensive review explores the intricate mechanisms of PANoptosis and its implications in cancer. PANoptosis, a convergence apoptosis, pyroptosis, necroptosis, plays crucial role cell death immune response regulation. The study delves into molecular pathways each mechanism their crosstalk within emphasizing shared components like caspases PANoptosome complex. It highlights significant various cancers, including respiratory, digestive, genitourinary, gliomas, breast showing impact on tumorigenesis patient survival rates. We further discuss interwoven relationship between tumor microenvironment (TME), illustrating how influences behavior progression. underscores dynamic interplay tumors microenvironments, focusing roles different cells interactions with cancer cells. Moreover, presents new breakthroughs therapy, potential targeting to enhance anti-tumor immunity. outlines strategies manipulate for therapeutic purposes, such as key signaling molecules caspases, NLRP3, RIPK1, RIPK3. novel treatments immunogenic PANoptosis-initiated therapies nanoparticle-based is also explored.
Language: Английский
Citations
33
Immunological Reviews, Journal Year: 2025, Volume and Issue: 329(1)
Published: Jan. 1, 2025
ABSTRACT Z‐nucleic acid binding protein 1 (ZBP1) is an innate immune sensor recognizing nucleic acids in Z‐conformation. Upon sensing, ZBP1 triggers activation, inflammation, and programmed cell death during viral infections, mice development, inflammation‐associated diseases. The Zα domains of sense promote RIP‐homotypic interaction motif (RHIM)‐dependent signaling complex assembly to mount inflammation. studies on spurred understanding the role Z‐form RNA DNA cellular physiological functions. In particular, short genomic segments, endogenous retroviral elements, 3′UTR regions are likely sources Z‐RNAs that orchestrate Recent seminal identify intriguing association with adenosine deaminase acting RNA‐1 (ADAR1), cyclic GMP‐AMP synthase (cGAS) regulating aberrant chronic cancer. Thus, attractive target aid development specific therapeutic regimes for disease biology. Here, we discuss Z‐RNA activation death, Also, how coordinates intracellular perturbations homeostasis, formation regulate diseases
Language: Английский
Citations
2
The Journal of Experimental Medicine, Journal Year: 2023, Volume and Issue: 220(8)
Published: July 14, 2023
Nucleic acid sensing is a central process in the immune system, with far-reaching roles antiviral defense, autoinflammation, and cancer. Z-DNA binding protein 1 (ZBP1) sensor for double-stranded DNA RNA helices unusual left-handed Z conformation termed Z-RNA. Recent research established ZBP1 as key upstream regulator of cell death proinflammatory signaling. Recognition Z-DNA/RNA by promotes host resistance to viral infection but can also drive detrimental autoinflammation. Additionally, has interesting cancer other disease settings emerging an attractive target therapy.
Language: Английский
Citations
39
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
Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 168, P. 115696 - 115696
Published: Oct. 12, 2023
Programmed cell death (PCD) is a key mechanism for the study of anticancer drugs and has significant impact on development management cancer. A growing amount data indicates that different kinds PCD, particularly pyroptosis, apoptosis, necroptosis, interact closely. Recent research revealed existence distinct inflammatory PCD modality known as PANoptosis, which controlled by complex PANoptosome complexes built combining elements from pathways. No single route sufficient to explain all physiologic effects seen in PANoptosis. Numerous studies have demonstrated PANoptosis can successfully stop cancer cells growing, proliferating, developing drug resistance. As result, it changed focus targeted therapy. In this review, we outlined molecular processes activation modulation well mechanisms innate immune death. order provide theoretical foundation targeting an anti-cancer target, also highlight PANoptosomes discovered date give overview implications treatment.
Language: Английский
Citations
26
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