Resolve: Mitochondrial DAMPs-Driven AIM2 Inflammasome Activation in Neurodegeneration

Auto-generated challenge from hypothesis h-var-6957745fea (composite_score=0.805). Target gene: AIM2/CASP1/IL1B/PYCARD. Source hypothesis title: Mitochondrial DAMPs-Driven AIM2 Inflammasome Activation in Neurodegeneration. Success criteria: 1. mtDNA copy number in cytoplasm increases >2-fold in disease-state microglia (AD tissue or LPS model). 2. AIM2 deficiency (KO microglia) reduces caspase-1 activation by >60% vs. WT. 3. IL-1beta release decreases by >50% in AIM2-KO vs. scramble in NLRP3/ AIM2 double-stimulated cells. 4. In vivo: AIM2 inhibitor reduces microglial caspase-1 activation by >40% and improves behavioral scores.

$250

OPEN

Confidence:

30%

Created: 2026-04-26

Linked Targets (4)

CASP1 Caspase-1 PDB:2HBQ0.57

🧬 View 3D Structure — PDB 2HBQ click to expand

PYCARD Apoptosis-associated speck-like protein containing CARD PDB:1UCP0.51

🧬 View 3D Structure — PDB 1UCP click to expand

IL1B Interleukin-1 beta PDB:1I1B0.65

🧬 View 3D Structure — PDB 1I1B click to expand

NLRP3 NACHT, LRR and PYD domains-containing protein 3 PDB:7LMZ0.64

🧬 View 3D Structure — PDB 7LMZ click to expand

Detected Targets:

CASP1 IL1B NLRP3

3D Protein Structure

▶ View 3D structure: CASP1 — PDB 1ICE

Experimental structure from RCSB PDB | Powered by Mol* | Rotate: click+drag | Zoom: scroll

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Linked Hypotheses (1)

Mitochondrial DAMPs-Driven AIM2 Inflammasome Activation in Neurodegeneration AIM2, CASP1, IL1B, PYCARD0.81