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Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
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The NLRP1 and CARD8 inflammasomes
Cornelius Y Taabazuing1, Andrew R Griswold2,3, Daniel A Bachovchin1,4,3
1Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Immunological Reviews
|June 20, 2020
Summary
NLRP1 and CARD8 inflammasomes activate inflammatory responses. Their activation involves proteasome-mediated degradation of N-terminal fragments, releasing C-terminal fragments to form inflammasomes, with roles in disease and metabolism.
Area of Science:
- Immunology
- Cellular Biology
Background:
- Inflammasomes are critical for innate immunity, responding to danger signals.
- NLRP1 and CARD8 are related inflammasome sensors with incompletely understood activation pathways.
Purpose of the Study:
- To review known activators and mechanistic insights of NLRP1 and CARD8 inflammasomes.
- To discuss disease-associated mutations and emerging roles in metabolism.
Main Methods:
- Literature review of inflammasome research.
- Analysis of post-translational modifications and protein degradation pathways.
Main Results:
- NLRP1 and CARD8 activation involves autoproteolysis and proteasome-mediated N-terminal fragment degradation.
- Diverse stimuli like toxins, pathogens, and small molecules activate these inflammasomes.
- Disease-associated mutations and metabolic links are increasingly recognized.
Conclusions:
- NLRP1 and CARD8 inflammasomes are regulated by proteasomal degradation of inhibitory fragments.
- Further research is needed to fully elucidate their biological functions and disease relevance.
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