Role of pyroptosis in the pathogenesis and treatment of diseases

Abstract

Programmed cell death (PCD) is regarded as a pathological form of cell death with an intracellular program mediated, which plays a pivotal role in maintaining homeostasis and embryonic development. Pyroptosis is a new paradigm of PCD, which has received increasing attention due to its close association with immunity and disease. Pyroptosis is a form of inflammatory cell death mediated by gasdermin that promotes the release of proinflammatory cytokines and contents induced by inflammasome activation. Recently, increasing evidence in studies shows that pyroptosis has a crucial role in inflammatory conditions like cardiovascular diseases (CVDs), cancer, neurological diseases (NDs), and metabolic diseases (MDs), suggesting that targeting cell death is a potential intervention for the treatment of these inflammatory diseases. Based on this, the review aims to identify the molecular mechanisms and signaling pathways related to pyroptosis activation and summarizes the current insights into the complicated relationship between pyroptosis and multiple human inflammatory diseases (CVDs, cancer, NDs, and MDs). We also discuss a promising novel strategy and method for treating these inflammatory diseases by targeting pyroptosis and focus on the pyroptosis pathway application in clinics.

B355252 Suppresses LPS-Induced Neuroinflammation in the Mouse Brain

“…B355252 suppressed TLR4, NLRP3, caspase-1, IL-1β, and IL-18 in LPS-injected animals, demonstrating that B355252 is capable of inhibiting the LPS-activated pyroptosis signaling pathway. Pyroptosis has been shown to be involved in the pathogenesis of cardiovascular diseases, metabolic diseases, and neurological diseases (for reviews, see [42][43][44][45][46][47][48]). In the nervous system, pyroptosis is associated with Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and cerebral stroke.…”

“…In the nervous system, pyroptosis is associated with Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and cerebral stroke. Therefore, pyroptosis has emerged as a novel therapeutic target for various diseases [48][49][50]. For example, activation of pyroptosis suppresses tumor growth and promotes anti-cancer drug sensitivity [51,52]; while inhibition of pyroptosis prevents neuronal death and improves behavioral performance in Parkinson's disease, Alzheimer's disease, ischemic stroke, traumatic brain and spinal cord injuries, and diabetic encephalopathy models [53][54][55][56][57][58][59][60][61].…”

Restraint Stress-Induced Immunosuppression Is Associated with Concurrent Macrophage Pyroptosis Cell Death in Mice

“…In our study, we also discovered a connection between pyroptosis, one of the regulated cell death pathways [ 41 , 42 , 43 , 44 , 45 ], and restraint-stress-induced immunosuppression. Pyroptosis is a highly inflammatory type of programmed cell death that occurs in response to infection or cellular damage [ 44 , 45 , 46 ]. It involves the activation of the inflammasome and its crucial component caspase-1, which initiates pyroptosis [ 44 , 45 , 46 ].…”

“…Pyroptosis is a highly inflammatory type of programmed cell death that occurs in response to infection or cellular damage [ 44 , 45 , 46 ]. It involves the activation of the inflammasome and its crucial component caspase-1, which initiates pyroptosis [ 44 , 45 , 46 ]. Certain treatments, such as canonical inflammasome NLRP3 inhibitors OLT1177 and caspase-1 inhibitor Z-WEHD-FMK, have been reported to block the cascade of events leading to pyroptosis and subsequent inflammation [ 41 , 42 , 43 , 46 , 47 , 48 ].…”

“…It involves the activation of the inflammasome and its crucial component caspase-1, which initiates pyroptosis [ 44 , 45 , 46 ]. Certain treatments, such as canonical inflammasome NLRP3 inhibitors OLT1177 and caspase-1 inhibitor Z-WEHD-FMK, have been reported to block the cascade of events leading to pyroptosis and subsequent inflammation [ 41 , 42 , 43 , 46 , 47 , 48 ]. However, the specific role of macrophage pyroptosis in restraint-stress-induced immunosuppression remains unclear and warrants further investigation.…”