The role of inflammasomes in human diseases and their potential as therapeutic targets

Abstract

Inflammasomes are large protein complexes that play a major role in sensing inflammatory signals and triggering the innate immune response. Each inflammasome complex has three major components: an upstream sensor molecule that is connected to a downstream effector protein such as caspase-1 through the adapter protein ASC. Inflammasome formation typically occurs in response to infectious agents or cellular damage. The active inflammasome then triggers caspase-1 activation, followed by the secretion of pro-inflammatory cytokines and pyroptotic cell death. Aberrant inflammasome activation and activity contribute to the development of diabetes, cancer, and several cardiovascular and neurodegenerative disorders. As a result, recent research has increasingly focused on investigating the mechanisms that regulate inflammasome assembly and activation, as well as the potential of targeting inflammasomes to treat various diseases. Multiple clinical trials are currently underway to evaluate the therapeutic potential of several distinct inflammasome-targeting therapies. Therefore, understanding how different inflammasomes contribute to disease pathology may have significant implications for developing novel therapeutic strategies. In this article, we provide a summary of the biological and pathological roles of inflammasomes in health and disease. We also highlight key evidence that suggests targeting inflammasomes could be a novel strategy for developing new disease-modifying therapies that may be effective in several conditions.

Sporadic Inclusion Body Myositis at the Crossroads between Muscle Degeneration, Inflammation, and Aging

“…Recently, the involvement of the NLRP3 inflammasome has been reported in sIBM [ 215 ]. The inflammasome pathway can be triggered by different endogenous or exogenous signals leading to the secretion of pro-inflammatory cytokines via caspase-1 activation [ 216 ]. Activation of the inflammasome pathway has been detected in response to intracellular aggregation of proteins and occurring in other protein aggregation diseases [ 217 , 218 ].…”

Atherosclerosis and Bidirectional Relationship between Cancer and Cardiovascular Disease: From Bench to Bedside—Part 1

“…The growth of an atherosclerotic plaque is a chronic dynamic inflammatory process with many different players. Early in the atherogenesis, high levels of oxidized low-density lipoproteins (ox-LDL) and remnants of triglyceride-rich lipoproteins gain access to the subendothelial space eliciting a danger signal that activate the NOD [nucleotide oligomerization domain]-,LRR[leucine-rich repeat]-,and PYD [pyrin domain]-containing protein3 (NLRP3) inflammasome [49,50] in innate immune cells. The activated inflammasome starts a cascade of inflammatory cytokines (IL-1β, IL-6) and upregulates highsensitivity C-reactive protein (hs-CRP) in the liver that eventually leads to atherosclerotic lesions.…”

Elucidating the role of Pyroptosis in papillary thyroid cancer: prognostic, immunological, and therapeutic perspectives

“…Pyroptosis is a newly discovered form of programmed cell death characterized by the formation of membrane pores, subsequent cell swelling and lysis, and the release of proinflammatory substances [ 4 ]. Its role in various human diseases and its potential as therapeutic targets have been widely studied [ 5 , 6 ]. Emerging evidence reveals that pyroptosis plays dual roles in cancer.…”

“…Emerging evidence reveals that pyroptosis plays dual roles in cancer. On the one hand, pyroptosis within the tumor immune microenvironment (TIME) generates inflammasomes and cytokines that may promote tumorigenesis, immunosuppression, angiogenesis, and metastasis [ 5 , 7 ]. On the other hand, pyroptosis triggers antitumor immunity by activating cytotoxic T cells, augmenting macrophage phagocytosis, and transforming “cold” tumors into “hot” tumors, thereby amplifying treatment-induced tumor cell death [ 6 , 8 ].…”