From the Guidelines
Several peptides can affect NLRP3 inflammasome activation, including MCC950, Oridonin, CY-09, Tranilast, and β-hydroxybutyrate (BHB), with the most recent evidence suggesting that these peptides are valuable in managing inflammatory conditions like gout, atherosclerosis, and neurodegenerative diseases where NLRP3 inflammasome activation contributes to pathology 1.
Peptides Affecting NLRP3 Activation
The peptides that can affect NLRP3 inflammasome activation include:
- MCC950: directly binds to the NLRP3 protein to prevent its activation
- Oridonin: covalently binds to cysteine residues in NLRP3, inhibiting its activation and subsequent inflammatory responses
- CY-09: specifically targets the ATP-binding motif of NLRP3, preventing its activation
- Tranilast: inhibits NLRP3 oligomerization, a critical step in inflammasome assembly
- β-hydroxybutyrate (BHB): a ketone body that inhibits NLRP3 activation by preventing potassium efflux and reducing ASC oligomerization
Mechanism of Action
These peptides work by inhibiting the activation of the NLRP3 inflammasome, which reduces the production of pro-inflammatory cytokines IL-1β and IL-18, key mediators of inflammation and tissue damage in conditions like gout, atherosclerosis, and neurodegenerative diseases 1.
Clinical Implications
The inhibition of NLRP3 activation by these peptides has significant clinical implications, as it may provide a therapeutic approach for managing inflammatory conditions where NLRP3 inflammasome activation contributes to pathology, as suggested by recent studies 1.
Recent Evidence
Recent evidence from 2022 suggests that the peptides mentioned above are effective in managing inflammatory conditions, with a focus on the diagnosis, management, and monitoring of interleukin-1 mediated autoinflammatory diseases 1.
From the Research
Peptides Affecting NLRP3 Activation
- The study 2 discusses the potential of peptides as therapeutic agents for modulating NLRP3 inflammasome activation, highlighting their advantages over small molecules, including higher selectivity and reduced toxicity.
- However, the provided studies do not specifically mention peptides that can affect NLRP3 activation, but rather focus on the mechanisms of NLRP3 inflammasome activation and its role in various diseases.
- The activation of NLRP3 is triggered by a drop in cytosolic K⁺, as shown in the study 3, but it does not mention peptides as a factor in this process.
- The review 4 discusses the regulatory mechanisms of NLRP3 inflammasome activation, including protein-protein interactions and posttranslational modifications, but does not mention specific peptides.
- The studies 5 and 6 discuss the differences in NLRP3 inflammasome responses to microbial and sterile signals, and the role of NLRP3 in inflammatory diseases, but do not provide information on peptides affecting NLRP3 activation.
Mechanisms of NLRP3 Activation
- The study 3 shows that a drop in cytosolic K⁺ is the common step necessary and sufficient for caspase-1 activation and NLRP3 inflammasome activation.
- The review 4 discusses the complex mechanisms regulating NLRP3 inflammasome activation, including priming/licensing and assembly steps.
- The study 5 found that NLRP3 inflammasome responses were weakest when both signal 1 and signal 2 were sterile, but responses were faster and stronger when at least one of the two signals was microbial.
- The review 6 discusses the recent advances in understanding the NLRP3 mechanism and its role in disease pathology, but does not provide information on peptides affecting NLRP3 activation.