Inflammasomes are cytosolic protein complexes that form in response to pathogen or damage signals and initiate inflammation. Signal transduction in the inflammasome pathway occurs via protein-protein interaction, protein conformational change, and oligomerization. Recent advances in structural biology have provided multiple insights in inflammasome regulation that are both biologically intriguing and therapeutically valuable. In this review, we summarize the current understanding of three most studied inflammasome complexes: the NAIP/NLRC4, NLRP1, and NLRP3 inflammasomes. We discuss the general mechanisms and unique features of their regulation and how investigating these systems may contribute to therapeutic applications.
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http://dx.doi.org/10.1016/j.sbi.2022.102390 | DOI Listing |
J Neuroinflammation
January 2025
Lanzhou University Second Hospital, 82 Cui-Ying-Men, Lanzhou, 730030, PR China.
Background: Intervertebral disc degeneration (IDD) is a leading cause of low back pain, often linked to inflammation and pyroptosis in nucleus pulposus (NP) cells. The role of Periostin (POSTN) in IDD remains unclear.
Objective: This study aims to investigate the influence of POSTN on pyroptosis and NLRP3 inflammasome activation in NP cells during IDD.
J Extracell Vesicles
January 2025
Institut de Recherche en Santé Digestive (IRSD), Université de Toulouse, INSERM, INRAE, ENVT, UPS, Toulouse, France.
CprA is a short-chain dehydrogenase/reductase (SDR) that contributes to resistance against colistin and antimicrobial peptides. The cprA gene is conserved across Pseudomonas aeruginosa clades and its expression is directly regulated by the two-component system PmrAB. We have shown that cprA expression leads to the production of outer membrane vesicles (OMVs) that block autophagic flux and have a greater capacity to activate the non-canonical inflammasome pathway.
View Article and Find Full Text PDFFront Immunol
January 2025
Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet and University of Oslo, Oslo, Norway.
Introduction: CD38, a regulator of intracellular calcium signalling, is highly expressed in immune cells. Mice lacking CD38 are very susceptible to acute bacterial infections, implicating CD38 in innate immune responses. The effects of CD38 inhibition on NLRP3 inflammasome activation in human primary monocytes and monocyte-derived macrophages have not been investigated.
View Article and Find Full Text PDFFront Med (Lausanne)
January 2025
Department of Dermatology, Paediatric Dermatology and Oncology, Medical University of Łódź, Łódź, Poland.
Introduction: Inflammasomes NLRP1 (NLR family pyrin domain containing 1) and NLRP3 are pivotal regulators of the innate immune response, activated by a spectrum of endogenous and exogenous stressors, including ultraviolet radiation (UVR). The precise molecular mechanisms underlying the activation of these inflammasomes remain unclear. Furthermore, the involvement of interleukin-33 (IL-33) in UVR-induced skin carcinogenesis is not well defined.
View Article and Find Full Text PDFBiochem Soc Trans
January 2025
School of Biosciences, University of Sheffield, Western Bank, Sheffield, S10 2TN, United Kingdom.
NLRP3 is an inflammasome seeding pattern recognition receptor that initiates a pro-inflammatory signalling cascade in response to changes in intracellular homeostasis that are indicative of bacterial infection or tissue damage. Several types of post-translational modification (PTM) have been identified that are added to NLRP3 to regulate its activity. Recent progress has revealed that NLRP3 is subject to a further type of PTM, S-acylation (or palmitoylation), which involves the reversible addition of long-chain fatty acids to target cysteine residues by opposing sets of enzymes.
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