Caspase-1 Summary:

Structure and Activation:

• Zymogen protein (pro-caspase)
• Activated within inflammasomes
• Contains CARD domain
• Requires specific structural rearrangement

Key Inflammatory Functions:

• Processes inflammatory proteins IL-1β and IL-18
• Triggers pyroptosis (programmed cell death)
• Cleaves Gasdermin D to form membrane pores
• Releases inflammatory cytokines

Inflammatory Mechanisms:

• Activated by pathogen and danger signals
• Involves ASC adaptor protein clustering
• Uses specific aspartate cleavage sites
• Modulated by post-translational modifications

Physiological Impacts:

• Promotes immune response
• Attracts neutrophils
• Stimulates natural killer and T-cell activity
• Helps eradicate pathogens

Therapeutic Potential:

• Target for inflammatory disease treatments
• Inhibition strategies under investigation
• Trials of caspase-1 inhibitors (e.g., VX-765)
• Focuses on modulating inflammasome formation

Significance: Critical molecular player in innate immune responses and inflammatory regulation.