Caspase ≈ Caspase
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Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases Open
Summary Cell death is a fundamental biological phenomenon that is essential for the survival and development of an organism. Emerging evidence also indicates that cell death contributes to immune defense against infectious diseases. Pyropt…
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Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies Open
Apoptosis is a form of programmed cell death that results in the orderly and efficient removal of damaged cells, such as those resulting from DNA damage or during development. Apoptosis can be triggered by signals from within the cell, suc…
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Apoptosis: A Target for Anticancer Therapy Open
Apoptosis, the cell’s natural mechanism for death, is a promising target for anticancer therapy. Both the intrinsic and extrinsic pathways use caspases to carry out apoptosis through the cleavage of hundreds of proteins. In cancer, the apo…
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Pathogen blockade of TAK1 triggers caspase-8–dependent cleavage of gasdermin D and cell death Open
Caspase-8 is a player in pyroptosis The activation of certain pattern-recognition receptors by pathogen-associated molecular patterns results in the formation of inflammasome complexes. Inflammasome complexes can initiate both the maturati…
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Inflammasome activation and regulation: toward a better understanding of complex mechanisms Open
Inflammasomes are cytoplasmic multiprotein complexes comprising a sensor protein, inflammatory caspases, and in some but not all cases an adapter protein connecting the two. They can be activated by a repertoire of endogenous and exogenous…
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Structural Mechanisms of NLRP3 Inflammasome Assembly and Activation Open
As an important sensor in the innate immune system, NLRP3 detects exogenous pathogenic invasions and endogenous cellular damage and responds by forming the NLRP3 inflammasome, a supramolecular complex that activates caspase-1. The three ma…
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GsdmD p30 elicited by caspase-11 during pyroptosis forms pores in membranes Open
Significance Pyroptosis is a form of cell death that is critical for eliminating innate immune cells infected with intracellular bacteria. Microbial products such as lipopolysaccharide, which is a component of Gram-negative bacteria, trigg…
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Apoptosis and apoptotic body: disease message and therapeutic target potentials Open
Apoptosis is widely known as programmed cell death eliciting no inflammatory responses. The intricacy of apoptosis has been a focus of an array of researches, accumulating a wealth of knowledge which led to not only a better understanding …
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Caspases in Cell Death, Inflammation, and Pyroptosis Open
Caspases are a family of conserved cysteine proteases that play key roles in programmed cell death and inflammation. In multicellular organisms, caspases are activated via macromolecular signaling complexes that bring inactive procaspases …
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Caspase-8 induces cleavage of gasdermin D to elicit pyroptosis during <i>Yersinia</i> infection Open
Significance Here we demonstrate that Yersinia YopJ-induced murine macrophage death involves caspase-8–induced cleavage of both gasdermin D (GSDMD) and gasdermin E (GSDME). The ensuing cell death is rapid, morphologically is similar to pyr…
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Understanding Apoptosis and Apoptotic Pathways Targeted Cancer Therapeutics Open
Various physiological processes involve appropriate tissue developmental process and homeostasis - the pathogenesis of several diseases connected with deregulatory apoptosis process. Apoptosis plays a crucial role in maintaining a balance …
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Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation Open
Gasdermin E (GSDME/DFNA5) cleavage by caspase-3 liberates the GSDME-N domain, which mediates pyroptosis by forming pores in the plasma membrane. Here we show that GSDME-N also permeabilizes the mitochondrial membrane, releasing cytochrome …
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Caspase‐8: regulating life and death Open
Summary Roles for cell death in development, homeostasis, and the control of infections and cancer have long been recognized. Although excessive cell damage results in passive necrosis, cells can be triggered to engage molecular programs t…
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ESCRT-dependent membrane repair negatively regulates pyroptosis downstream of GSDMD activation Open
Fine-tuning pyroptosis with ESCRT-III Pyroptosis is an inflammatory form of cell death induced by select caspases downstream of inflammasome complexes. These caspases cleave gasdermin D (GSDMD), whose N-terminal fragments quickly form larg…
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MOMP, cell suicide as a BCL-2 family business Open
Apoptosis shapes development and differentiation, has a key role in tissue homeostasis, and is deregulated in cancer. In most cases, successful apoptosis is triggered by mitochondrial outer membrane permeabilization (MOMP), which defines t…
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Caspase-1 self-cleavage is an intrinsic mechanism to terminate inflammasome activity Open
Host-protective caspase-1 activity must be tightly regulated to prevent pathology, but mechanisms controlling the duration of cellular caspase-1 activity are unknown. Caspase-1 is activated on inflammasomes, signaling platforms that facili…
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Caspase-1 inhibition prevents glial inflammasome activation and pyroptosis in models of multiple sclerosis Open
Significance The pore-forming protein gasdermin D (GSDMD) was recently identified as the principal executioner of pyroptosis (“fiery death”), a type of proinflammatory programmed cell death driven by inflammasomes. Caspase-1 cleaves GSDMD,…
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Caspase-11–mediated endothelial pyroptosis underlies endotoxemia-induced lung injury Open
Acute lung injury is a leading cause of death in bacterial sepsis due to the wholesale destruction of the lung endothelial barrier, which results in protein-rich lung edema, influx of proinflammatory leukocytes, and intractable hypoxemia. …
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Inflammasome activation and assembly at a glance Open
Inflammasomes are multimeric protein complexes that typically comprise a sensor, an adaptor and the zymogen procaspase-1. An inflammasome assembles in response to a diverse range of pathogen-associated or danger-associated molecular patter…
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Paradoxical roles of caspase-3 in regulating cell survival, proliferation, and tumorigenesis Open
Caspase-3 is a widely expressed member of a conserved family of proteins, generally recognized for their activated proteolytic roles in the execution of apoptosis in cells responding to specific extrinsic or intrinsic inducers of this mode…
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Gasdermin D Exerts Anti-inflammatory Effects by Promoting Neutrophil Death Open
Gasdermin D (GSDMD) is considered a proinflammatory factor that mediates pyroptosis in macrophages to protect hosts from intracellular bacteria. Here, we reveal that GSDMD deficiency paradoxically augmented host responses to extracellular …
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A nuclease that mediates cell death induced by DNA damage and poly(ADP-ribose) polymerase-1 Open
DNA damage-activated nuclease identified Cells that experience stresses and accumulate excessive damage to DNA undergo cell death mediated by a nuclear enzyme known as PARP-1. During this process, apoptosis-inducing factor (AIF) translocat…
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Mitochondrial ROS promote macrophage pyroptosis by inducing GSDMD oxidation Open
Disrupted mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) generation are often associated with macrophage pyroptosis. It remains unclear how these forms of mitochondrial dysfunction relate to inflammasome activatio…
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Caspase-9: structure, mechanisms and clinical application Open
As the most intensively studied initiator caspase, caspase-9 is a key player in the intrinsic or mitochondrial pathway which is involved in various stimuli, including chemotherapies, stress agents and radiation. Caspase-9 is activated on t…
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Polyphyllin VI Induces Caspase-1-Mediated Pyroptosis via the Induction of ROS/NF-κB/NLRP3/GSDMD Signal Axis in Non-Small Cell Lung Cancer Open
Trillium tschonoskii Maxim (TTM), a traditional Chinese medicine, has been demonstrated to have a potent anti-tumor effect. Recently, polyphyllin VI (PPVI), a main saponin isolated from TTM, was reported by us to significantly suppress the…
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Chemotherapy-induced pyroptosis is mediated by BAK/BAX-caspase-3-GSDME pathway and inhibited by 2-bromopalmitate Open
Many chemotherapy treatments induce apoptosis or pyroptosis through BAK/BAX-dependent mitochondrial pathway. BAK/BAX activation causes the mitochondrial outer membrane permeabilization (MOMP), which induces the activation of pro-apoptotic …
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Influence of doxorubicin on apoptosis and oxidative stress in breast cancer cell lines Open
Breast cancer is one of the leading causes of mortality among women worldwide due to aggressive behavior, early metastasis, resistance to existing chemotherapeutic agent and high mortality rate. Doxorubicin (Dox) is a powerful antitumoral …
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N-terminal degradation activates the NLRP1B inflammasome Open
Degradation triggers the alarm Inflammasomes are multiprotein complexes that orchestrate proinflammatory cytokine secretion and cell death. Proteases such as anthrax lethal factor can activate an inflammasome known as NLRP1B, but the mecha…
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Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis proteins (IAPs) Open
Inhibitors of apoptosis (IAPs) are a family of proteins that play a significant role in the control of programmed cell death (PCD). PCD is essential to maintain healthy cell turnover within tissue but also to fight disease or infection. Un…
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Potential of apoptotic pathway-targeted cancer therapeutic research: Where do we stand? Open
Underneath the intricacy of every cancer lies mysterious events that impel the tumour cell and its posterity into abnormal growth and tissue invasion. Oncogenic mutations disturb the regulatory circuits responsible for the governance of ve…