NLRP3 Inflammasome Assembly Project
Overview
The NLRP3 inflammasome is a multiprotein complex that activates inflammatory caspases in response to diverse danger signals, leading to IL-1β/IL-18 release and pyroptotic cell death. Recent discoveries have clarified activation mechanisms and identified new regulators.
Model Species
Primary: Homo sapiens (human)
- Major therapeutic target
- Autoinflammatory disease relevance
Core Pathway Architecture
1. Sensor
- NLRP3 - NOD-like receptor, sensor component
2. Adaptor
- PYCARD (ASC) - Adaptor with PYD and CARD domains
3. Effector Caspases
- CASP1 - Caspase-1, cleaves pro-IL-1β
- CASP4/5 - Non-canonical inflammasome
4. Substrates/Outputs
- IL1B - Pro-inflammatory cytokine
- IL18 - Pro-inflammatory cytokine
- GSDMD - Gasdermin D, pore-forming executioner
5. Critical Regulators
- NEK7 - Essential NLRP3 activator (discovered 2016)
- BRCC3 - Deubiquitinase
- Various negative regulators
6. Priming/Licensing
- NFKB pathway - Transcriptional priming
Candidate Genes (~12-15)
| Gene | UniProt | Function |
|---|---|---|
| NLRP3 | Q96P20 | Sensor |
| PYCARD | Q9ULZ3 | ASC adaptor |
| CASP1 | P29466 | Effector caspase |
| CASP4 | P49662 | Non-canonical |
| CASP5 | P51878 | Non-canonical |
| GSDMD | P57764 | Pore formation |
| IL1B | P01584 | Cytokine |
| IL18 | Q14116 | Cytokine |
| NEK7 | Q8TDX7 | Essential activator |
| BRCC3 | P46736 | Deubiquitinase |
Key Recent Discoveries (2020+)
- Trans-Golgi network as NLRP3 activation site
- Post-translational modifications regulating assembly
- Structural basis of inflammasome assembly
- GSDMD pore structure
Disease Relevance
- CAPS (Cryopyrin-associated periodic syndromes)
- Gout, atherosclerosis
- Alzheimer's disease
- COVID-19 severity
Project Status
- [ ] Stub - needs gene folder setup