This challenge targets the hypothesis: **Astrocyte C3aR Signaling as Bifurcation Point for A1/A2 Fate** **Hypothesis Summary:** ## Mechanistic Overview Astrocyte C3aR Signaling as Bifurcation Point for A1/A2 Fate starts from the claim that modulating C3, C3aR, NFKB1, PPARGC1A within the disease context of Alzheimer's disease, Parkinson's disease can redirect a disease-relevant process. The original description reads: "## Mechanistic Overview Astrocyte C3aR Signaling as Bifurcation Point for A1/A2 Fate starts from the claim that modulating C3, C3aR, NFKB1, PPARGC1A within the disease context of Alzheimer's disease, Parkin **Falsifiable Predictions:** 1. Pharmacological modulation of C3 will alter Alzheimer's disease, Parkinson's disease markers in validated models by ≥20% 2. Genetic knockdown of the key target will reproduce the pathological phenotype in ≥2 independent model systems 3. Patient-derived biosamples will show the predicted molecular signature (sensitivity ≥70%, specificity ≥70%) 4. Mechanistic intervention at the proposed node will rescue neuronal viability in vitro by ≥30% **Bounty Tier:** $124,880 USD (composite score 0.749) **Challenge Type:** Open — any team may submit experimental evidence supporting or refuting this hypothesis **Success Criteria:** Peer-reviewed evidence demonstrating mechanistic validation of ≥2 of the 4 predictions, with independent replication.