Inhibitors of NLRP3 Inflammasome in Ischemic Heart Disease: Focus on Functional and Redox Aspects
Abstract
:1. Introduction
MIRI Activates Various Cell Death Pathways
2. Mechanisms Involved in MIRI and Interactions with NLRP3
2.1. Production of ROS
2.2. Calcium Overload
2.3. Role of mPTP Opening
2.4. Endothelial Dysfunction
3. Role for microRNAs in MIRI and NLRP3 Activation
4. Inflammasome and Redox Signaling
5. Inhibitors of NLRP3
6. Conclusions and Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Inhibitors | Links | Mechanisms | Refs. |
---|---|---|---|
Priming | |||
Curcumin | NF-κB | Reduce K+ flow, blocking the of ASC | [57] |
Bay 11-7082 | IKK-β | IKK-β induces phosphorylation and degradation of IκB proteins. IκB bind to NF-κB and prevent its translocation to the nucleus. The phosphorylation leads to the ubiquitination and proteasomal degradation of IκB, allowing NF-κB to be released and translocate to the nucleus. | [77,78,79] |
Activating Mechanism | |||
Colchicine | ATP-gated cation channels (P2X2/P2X7); Lysosome; ASC | P2X2/P2X7 receptor binds extracellular ATP with opening of the channel (K+ channel); damage to lysosome induce K+ outflow; ASC polymers bind to pro-caspase-1 causing its polymerization. The pro-caspase polymers will be activated by the structure itself that has formed; the caspase-1 produced will activate the subsequent components (IL-1β and IL-18) and form the GSDMD pores responsible for pyroptosis. | [59,60,61,62] |
INF4E, OLT1177, MCC950 and Bay 11-7082 | ATPase domain, NACHT domain | The specific function of ATP hydrolysis is yet unknown, it allows the subsequent interaction between NLRP3 and ASC. Reduce redox damage, increase SOD activity | [57,70,71] |
Glibenclamide/ Glyburide | NF-κB, NLRP3 oligomerization | Reduce the activation of NF-κB, expression/activation of NOX2 and iNOS, block the ADP-ATP switch in order to generate an active multimeric structure. | [66,67,68] |
1,2,4-Triazine Derivatives. | Blockade of IL-18, IL-1α and IL-1β; prevents SOD2 degradation; | [82,83,84,85] |
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Pagliaro, P.; Penna, C. Inhibitors of NLRP3 Inflammasome in Ischemic Heart Disease: Focus on Functional and Redox Aspects. Antioxidants 2023, 12, 1396. https://doi.org/10.3390/antiox12071396
Pagliaro P, Penna C. Inhibitors of NLRP3 Inflammasome in Ischemic Heart Disease: Focus on Functional and Redox Aspects. Antioxidants. 2023; 12(7):1396. https://doi.org/10.3390/antiox12071396
Chicago/Turabian StylePagliaro, Pasquale, and Claudia Penna. 2023. "Inhibitors of NLRP3 Inflammasome in Ischemic Heart Disease: Focus on Functional and Redox Aspects" Antioxidants 12, no. 7: 1396. https://doi.org/10.3390/antiox12071396