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Cellular & Molecular Immunology May 2021Cell death is a fundamental physiological process in all living organisms. Its roles extend from embryonic development, organ maintenance, and aging to the coordination... (Review)
Review
Cell death is a fundamental physiological process in all living organisms. Its roles extend from embryonic development, organ maintenance, and aging to the coordination of immune responses and autoimmunity. In recent years, our understanding of the mechanisms orchestrating cellular death and its consequences on immunity and homeostasis has increased substantially. Different modalities of what has become known as 'programmed cell death' have been described, and some key players in these processes have been identified. We have learned more about the intricacies that fine tune the activity of common players and ultimately shape the different types of cell death. These studies have highlighted the complex mechanisms tipping the balance between different cell fates. Here, we summarize the latest discoveries in the three most well understood modalities of cell death, namely, apoptosis, necroptosis, and pyroptosis, highlighting common and unique pathways and their effect on the surrounding cells and the organism as a whole.
Topics: Animals; Apoptosis; Health; Humans; Inflammation; Models, Biological; Necroptosis; Pyroptosis
PubMed: 33785842
DOI: 10.1038/s41423-020-00630-3 -
Cell Jan 2024Cell death supports morphogenesis during development and homeostasis after birth by removing damaged or obsolete cells. It also curtails the spread of pathogens by... (Review)
Review
Cell death supports morphogenesis during development and homeostasis after birth by removing damaged or obsolete cells. It also curtails the spread of pathogens by eliminating infected cells. Cell death can be induced by the genetically programmed suicide mechanisms of apoptosis, necroptosis, and pyroptosis, or it can be a consequence of dysregulated metabolism, as in ferroptosis. Here, we review the signaling mechanisms underlying each cell-death pathway, discuss how impaired or excessive activation of the distinct cell-death processes can promote disease, and highlight existing and potential therapies for redressing imbalances in cell death in cancer and other diseases.
Topics: Humans; Apoptosis; Cell Death; Ferroptosis; Homeostasis; Pyroptosis; Signal Transduction
PubMed: 38242081
DOI: 10.1016/j.cell.2023.11.044 -
Nature Reviews. Immunology Apr 2020The clearance of apoptotic cells by professional and non-professional phagocytes - a process termed 'efferocytosis' - is essential for the maintenance of tissue... (Review)
Review
The clearance of apoptotic cells by professional and non-professional phagocytes - a process termed 'efferocytosis' - is essential for the maintenance of tissue homeostasis. Accordingly, defective efferocytosis underlies a growing list of chronic inflammatory diseases. Although much has been learnt about the mechanisms of apoptotic cell recognition and uptake, several key areas remain incompletely understood. This Review focuses on new discoveries related to how phagocytes process the metabolic cargo they receive during apoptotic cell uptake; the links between efferocytosis and the resolution of inflammation in health and disease; and the roles of efferocytosis in host defence. Understanding these aspects of efferocytosis sheds light on key physiological and pathophysiological processes and suggests novel therapeutic strategies for diseases driven by defective efferocytosis and impaired inflammation resolution.
Topics: Apoptosis; Homeostasis; Humans; Inflammation; Phagocytes; Phagocytosis
PubMed: 31822793
DOI: 10.1038/s41577-019-0240-6 -
Brazilian Journal of Biology = Revista... 2021Apoptosis is a sequential order of cell death occurring regularly to ensure a homeostatic balance between the rate of cell formation and cell death. However, a misplaced... (Review)
Review
Apoptosis is a sequential order of cell death occurring regularly to ensure a homeostatic balance between the rate of cell formation and cell death. However, a misplaced of this balancing function can contribute to an abnormal cell growth / proliferation or autoimmune disorders etc. Apoptosis is therefore said to be crucial from the point of development of an embryo throughout the growth of an organism contributing to the renewal of tissues and also the getting rid of inflammatory cells. This review seeks to elaborate on the recent overview of the mechanism involved in apoptosis, some element and signal contributing to its function and inhibition together with how their malfunction contribute to a number of cancer related cases.
Topics: Apoptosis
PubMed: 33111928
DOI: 10.1590/1519-6984.228437 -
Cells Apr 2022Autophagy and apoptosis represent two fundamental pathophysiological mechanisms of cell fate regulation. However, the signaling pathways of these processes are...
Autophagy and apoptosis represent two fundamental pathophysiological mechanisms of cell fate regulation. However, the signaling pathways of these processes are significantly interconnected through various mechanisms of crosstalk. Indeed, autophagy/apoptosis crosstalk is still an emerging field, in which an increasing number of molecules are involved, including, for example, PINK1 and ERLINs. On the other hand, this crosstalk involves signal transduction pathways which are strongly dependent on Ca. Interestingly, crosstalk between autophagy and apoptosis impacts several pathologies, including multiple rheumatic diseases. The purpose of this Special Issue is also to investigate the bioactive properties of drugs with antitumor activity, focusing particularly on the role of anthraquinone derivatives in the regulation of cell death and autophagy crosstalk. This Special Issue of brings together the most recent advances in understanding the various aspects of crosstalk between autophagy and apoptosis and the interconnected signaling pathways, implying therapeutic perspectives for the utility of its modulation in an anti-cancer setting.
Topics: Apoptosis; Autophagy; Humans; Neoplasms; Signal Transduction
PubMed: 35563785
DOI: 10.3390/cells11091479 -
Immunological Reviews Sep 2020ZBP1 has been characterized as a critical innate immune sensor of not only viral RNA products but also endogenous nucleic acid ligands. ZBP1 sensing of the Z-RNA... (Review)
Review
ZBP1 has been characterized as a critical innate immune sensor of not only viral RNA products but also endogenous nucleic acid ligands. ZBP1 sensing of the Z-RNA produced during influenza virus infection induces cell death in the form of pyroptosis, apoptosis, and necroptosis (PANoptosis). PANoptosis is a coordinated cell death pathway that is driven through a multiprotein complex called the PANoptosome and enables crosstalk and co-regulation among these processes. During influenza virus infection, a key step in PANoptosis and PANoptosome assembly is the formation of the ZBP1-NLRP3 inflammasome. When Z-RNA is sensed, ZBP1 recruits RIPK3 and caspase-8 to activate the ZBP1-NLRP3 inflammasome. Several other host factors have been found to be important for ZBP1-NLRP3 inflammasome assembly, including molecules involved in the type I interferon signaling pathway and caspase-6. Additionally, influenza viral proteins, such as M2, NS1, and PB1-F2, have also been shown to regulate the ZBP1-NLRP3 inflammasome. This review explains the functions of ZBP1 and the mechanistic details underlying the activation of the ZBP1-NLRP3 inflammasome and the formation of the PANoptosome. Improved understanding of the ZBP1-NLRP3 inflammasome will direct the development of therapeutic strategies to target infectious and inflammatory diseases.
Topics: Apoptosis; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Necroptosis; Pyroptosis; RNA-Binding Proteins
PubMed: 32729116
DOI: 10.1111/imr.12909 -
Experimental & Molecular Medicine Feb 2022High mobility group box 1 (HMGB1) is a nonhistone nuclear protein that has multiple functions according to its subcellular location. In the nucleus, HMGB1 is a DNA... (Review)
Review
High mobility group box 1 (HMGB1) is a nonhistone nuclear protein that has multiple functions according to its subcellular location. In the nucleus, HMGB1 is a DNA chaperone that maintains the structure and function of chromosomes. In the cytoplasm, HMGB1 can promote autophagy by binding to BECN1 protein. After its active secretion or passive release, extracellular HMGB1 usually acts as a damage-associated molecular pattern (DAMP) molecule, regulating inflammation and immune responses through different receptors or direct uptake. The secretion and release of HMGB1 is fine-tuned by a variety of factors, including its posttranslational modification (e.g., acetylation, ADP-ribosylation, phosphorylation, and methylation) and the molecular machinery of cell death (e.g., apoptosis, pyroptosis, necroptosis, alkaliptosis, and ferroptosis). In this minireview, we introduce the basic structure and function of HMGB1 and focus on the regulatory mechanism of HMGB1 secretion and release. Understanding these topics may help us develop new HMGB1-targeted drugs for various conditions, especially inflammatory diseases and tissue damage.
Topics: Alarmins; Apoptosis; Autophagy; Cell Death; HMGB1 Protein
PubMed: 35217834
DOI: 10.1038/s12276-022-00736-w -
Journal of Hematology & Oncology Dec 2022Many types of human cells self-destruct to maintain biological homeostasis and defend the body against pathogenic substances. This process, called regulated cell death... (Review)
Review
Many types of human cells self-destruct to maintain biological homeostasis and defend the body against pathogenic substances. This process, called regulated cell death (RCD), is important for various biological activities, including the clearance of aberrant cells. Thus, RCD pathways represented by apoptosis have increased in importance as a target for the development of cancer medications in recent years. However, because tumor cells show avoidance to apoptosis, which causes treatment resistance and recurrence, numerous studies have been devoted to alternative cancer cell mortality processes, namely necroptosis, pyroptosis, ferroptosis, and cuproptosis; these RCD modalities have been extensively studied and shown to be crucial to cancer therapy effectiveness. Furthermore, evidence suggests that tumor cells undergoing regulated death may alter the immunogenicity of the tumor microenvironment (TME) to some extent, rendering it more suitable for inhibiting cancer progression and metastasis. In addition, other types of cells and components in the TME undergo the abovementioned forms of death and induce immune attacks on tumor cells, resulting in enhanced antitumor responses. Hence, this review discusses the molecular processes and features of necroptosis, pyroptosis, ferroptosis, and cuproptosis and the effects of these novel RCD modalities on tumor cell proliferation and cancer metastasis. Importantly, it introduces the complex effects of novel forms of tumor cell death on the TME and the regulated death of other cells in the TME that affect tumor biology. It also summarizes the potential agents and nanoparticles that induce or inhibit novel RCD pathways and their therapeutic effects on cancer based on evidence from in vivo and in vitro studies and reports clinical trials in which RCD inducers have been evaluated as treatments for cancer patients. Lastly, we also summarized the impact of modulating the RCD processes on cancer drug resistance and the advantages of adding RCD modulators to cancer treatment over conventional treatments.
Topics: Humans; Cell Death; Neoplasms; Copper; Apoptosis; Ferroptosis; Pyroptosis; Necroptosis
PubMed: 36482419
DOI: 10.1186/s13045-022-01392-3 -
Pharmacology & Therapeutics Apr 2022Programmed cell death (PCD) is an essential part of organismal development and plays fundamental roles in host defense against pathogens and the maintenance of... (Review)
Review
Programmed cell death (PCD) is an essential part of organismal development and plays fundamental roles in host defense against pathogens and the maintenance of homeostasis. However, excess activation of PCD pathways has proven to be detrimental and can drive disease. Additionally, resistance to PCD can also contribute to disease development. Modulation of PCD, therefore, has great therapeutic potential in a wide range of diseases, including infectious, neurodegenerative, autoinflammatory, and metabolic diseases and cancer. Nevertheless, manipulation of cell death and inflammation for therapeutic intervention is a delicate process, highly specific to the context of the disease of interest, making the selection of the appropriate target molecule crucially important. Several PCD pathways are associated with innate immunity, including pyroptosis, apoptosis, necroptosis, and PANoptosis, which is defined as an inflammatory PCD pathway with key features of pyroptosis, apoptosis, and/or necroptosis that cannot be accounted for by any of these three PCD pathways alone. All of these PCD pathways are regulated by upstream sensors and signaling cascades that assemble multimeric complexes to serve as activation platforms for downstream molecules; these sensors and signaling molecules provide attractive target points for therapeutic intervention. Here, we discuss the molecular mechanisms of innate immune-mediated cell death in health and disease, with a particular focus on the molecules putatively involved in the formation of the PANoptosome and the induction of inflammatory cell death. Further, we discuss the implications and feasibility of targeting these molecules to improve disease outcomes, as well as current clinical approaches.
Topics: Apoptosis; Cell Death; Humans; Immunity, Innate; Necroptosis; Pyroptosis
PubMed: 34619283
DOI: 10.1016/j.pharmthera.2021.108010 -
Cell Death & Disease May 2022The concept of cell death has been expanded beyond apoptosis and necrosis to additional forms, including necroptosis, pyroptosis, autophagy, and ferroptosis. These cell... (Review)
Review
The concept of cell death has been expanded beyond apoptosis and necrosis to additional forms, including necroptosis, pyroptosis, autophagy, and ferroptosis. These cell death modalities play a critical role in all aspects of life, which are noteworthy for their diverse roles in diseases. Atherosclerosis (AS) and vascular calcification (VC) are major causes for the high morbidity and mortality of cardiovascular disease. Despite considerable advances in understanding the signaling pathways associated with AS and VC, the exact molecular basis remains obscure. In the article, we review the molecular mechanisms that mediate cell death and its implications for AS and VC. A better understanding of the mechanisms underlying cell death in AS and VC may drive the development of promising therapeutic strategies.
Topics: Apoptosis; Atherosclerosis; Ferroptosis; Humans; Pyroptosis; Vascular Calcification
PubMed: 35585052
DOI: 10.1038/s41419-022-04923-5