Emerging connectivity of programmed cell death pathways and its physiological implications

Nature Reviews Molecular Cell Biology, Journal Year: 2020, Volume and Issue: 21(11), P. 678 - 695

Published: Sept. 1, 2020

Language: Английский

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The regulation of the ZBP1‐NLRP3 inflammasome and its implications in pyroptosis, apoptosis, and necroptosis (PANoptosis)

Immunological Reviews, Journal Year: 2020, Volume and Issue: 297(1), P. 26 - 38

Published: July 29, 2020

Abstract ZBP1 has been characterized as a critical innate immune sensor of not only viral RNA products but also endogenous nucleic acid ligands. sensing the Z‐RNA produced during influenza virus infection induces cell death in form pyroptosis, apoptosis, and necroptosis (PANoptosis). PANoptosis is coordinated pathway that driven through multiprotein complex called PANoptosome enables crosstalk co‐regulation among these processes. During infection, key step assembly formation ZBP1‐NLRP3 inflammasome. When sensed, recruits RIPK3 caspase‐8 to activate Several other host factors have found be important for inflammasome assembly, including molecules involved type I interferon signaling caspase‐6. Additionally, proteins, such M2, NS1, PB1‐F2, shown regulate This review explains functions mechanistic details underlying activation PANoptosome. Improved understanding will direct development therapeutic strategies target infectious inflammatory diseases.

Language: Английский

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From pyroptosis, apoptosis and necroptosis to PANoptosis: A mechanistic compendium of programmed cell death pathways

Computational and Structural Biotechnology Journal, Journal Year: 2021, Volume and Issue: 19, P. 4641 - 4657

Published: Jan. 1, 2021

Pyroptosis, apoptosis and necroptosis are the most genetically well-defined programmed cell death (PCD) pathways, they intricately involved in both homeostasis disease. Although identification of key initiators, effectors executioners each these three PCD pathways has historically delineated them as distinct, growing evidence highlighted extensive crosstalk among them. These observations have led to establishment concept PANoptosis, defined an inflammatory pathway regulated by PANoptosome complex with features pyroptosis, and/or that cannot be accounted for any alone. In this review, we provide a brief overview research history necroptosis. We then examine intricate discuss current PANoptosis. also detail molecular assembly complex, scaffold contemporaneous engagement molecules from apoptosis, PANoptosis is now known critically many diseases, including infection, sterile inflammation cancer, future discovery novel PANoptotic components will continue broaden our understanding fundamental processes inform development new therapeutics.

Language: Английский

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Influenza virus and SARS-CoV-2: pathogenesis and host responses in the respiratory tract

Nature Reviews Microbiology, Journal Year: 2021, Volume and Issue: 19(7), P. 425 - 441

Published: April 6, 2021

Influenza viruses cause annual epidemics and occasional pandemics of respiratory tract infections that produce a wide spectrum clinical disease severity in humans. The novel betacoronavirus severe acute syndrome coronavirus 2 (SARS-CoV-2) emerged December 2019 has since caused pandemic. Both viral host factors determine the extent virus-induced lung damage. host's response to infection is necessary for clearance but may be deleterious contribute phenotypes. Similarly, tissue repair mechanisms are required recovery from across severity; however, dysregulated responses lead chronic dysfunction. Understanding immunopathology following lower broaden treatment options. In this Review, we discuss pathogenesis, contribution phenotypes highlight early late epithelial influenza virus infection, each which been well characterized. Although still learning about SARS-CoV-2 its manifestations humans, throughout Review what known context broad knowledge virus, highlighting similarities differences between viruses. Schultz-Cherry, Thomas colleagues pathogenesis human tract, disease, current potential future therapies infections.

Language: Английский

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ADAR1 masks the cancer immunotherapeutic promise of ZBP1-driven necroptosis

Nature, Journal Year: 2022, Volume and Issue: 606(7914), P. 594 - 602

Published: May 25, 2022

Language: Английский

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ADAR1 restricts ZBP1-mediated immune response and PANoptosis to promote tumorigenesis

Cell Reports, Journal Year: 2021, Volume and Issue: 37(3), P. 109858 - 109858

Published: Oct. 1, 2021

Cell death provides host defense and maintains homeostasis. Zα-containing molecules are essential for these processes. Z-DNA binding protein 1 (ZBP1) activates inflammatory cell death, PANoptosis, whereas adenosine deaminase acting on RNA (ADAR1) serves as an editor to maintain Here, we identify characterize ADAR1's interaction with ZBP1, defining its role in regulation tumorigenesis. Combining interferons (IFNs) nuclear export inhibitors (NEIs) ZBP1-dependent PANoptosis. ADAR1 suppresses this PANoptosis by interacting the Zα2 domain of ZBP1 limit RIPK3 interactions. Adar1

Language: Английский

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Impaired type I interferon activity and exacerbated inflammatory responses in severe Covid-19 patients

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2020, Volume and Issue: unknown

Published: April 23, 2020

Abstract Background Coronavirus disease 2019 (Covid-19) is a major global threat that has already caused more than 100,000 deaths worldwide. It characterized by distinct patterns of progression implying diverse host immune response. However, the immunological features and molecular mechanisms involved in Covid-19 severity remain so far poorly known. Methods We performed an integrated analysis included in-depth phenotypical profiling cells, whole-blood transcriptomic cytokine quantification on cohort fifty Covid19 patients with spectrum severity. All patient were tested 8 to 12 days following first symptoms absence anti-inflammatory therapy. Results A unique phenotype severe critically ill was identified. consists profoundly impaired interferon (IFN) type I response low production activity, consequent downregulation interferon-stimulated genes. This associated persistent blood virus load exacerbated inflammatory partially driven transcriptional factor NFĸB. also increased tumor necrosis (TNF)-α interleukin (IL)-6 signaling as well innate chemokines. Conclusion propose type-I IFN deficiency hallmark could identify define high-risk population. Our study provides rationale for testing administration combined adapted therapy targeting IL-6 or TNF-α most patients. These data raise concern utilization drugs interfere pathway.

Language: Английский

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Apoptotic cell death in disease—Current understanding of the NCCD 2023

Cell Death and Differentiation, Journal Year: 2023, Volume and Issue: 30(5), P. 1097 - 1154

Published: April 26, 2023

Language: Английский

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Functional landscape of SARS-CoV-2 cellular restriction

Molecular Cell, Journal Year: 2021, Volume and Issue: 81(12), P. 2656 - 2668.e8

Published: April 15, 2021

Language: Английский

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Necrostatin-1 and necroptosis inhibition: Pathophysiology and therapeutic implications

Pharmacological Research, Journal Year: 2020, Volume and Issue: 163, P. 105297 - 105297

Published: Nov. 9, 2020

Language: Английский

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