Abstract
Programmed Cell Death (PCD) is considered to be a pathological form of cell death when mediated by an intracellular program and it balances cell death with survival of normal cells. Pyroptosis, a type of PCD, is induced by the inflammatory caspase cleavage of gasdermin D (GSDMD) and apoptotic caspase cleavage of gasdermin E (GSDME). This review aims to summarize the latest molecular mechanisms about pyroptosis mediated by pore-forming GSDMD and GSDME proteins that permeabilize plasma and mitochondrial membrane activating pyroptosis and apoptosis. We also discuss the potentiality of pyroptosis as a therapeutic target in human diseases. Blockade of pyroptosis by compounds can treat inflammatory disease and pyroptosis activation contributes to cancer therapy.
Highlights
Many disease states are cross-linked with cell death
Pyroptosis is induced by members of the gasdermin superfamily, including GSDMA, GSDMB, GSDMC, gasdermin D (GSDMD) and gasdermin E (GSDME) [25,26,27,28,29,30], of which, GSDMD and GSDME are widely studied in pyroptosis
Pyroptosis is a new form of programmed cell death and has recently been extensively studied in various diseases
Summary
Many disease states are cross-linked with cell death. The Nomenclature Committee on Cell Death make a series of recommendations to systematically classify cell death [1,2]. Programmed Cell Death (PCD) is mediated by specific cellular mechanisms and some signaling pathways are activated in these processes [3]. Autophagy and programmed necrosis are the three main types of PCD [4], and they may jointly determine the fate of malignant tumor cells. Pyroptosis is a form of programmed necrosis and was firstly described in myeloid cells infected by pathogens or bacteria in 1992 [5,6,7]. Pyroptotic death is an inflammatory form of PCD characterized by cellular swelling and rupture, lysis and release of pro-inflammatory molecules such as Interleukin 1β and Interleukin 18 (IL-1β and IL-18) [9,10]. Pyroptotic death is often harmful to normal tissues, it can be beneficial to cancer treatment. We summarize and discuss the potential effects of pyroptosis in inflammatory diseases and anticancer therapy
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