This challenge targets the hypothesis: **PDE4 Inhibition as Inflammatory Reset for PD Oligodendrocytes** **Hypothesis Summary:** ## Mechanistic Overview PDE4 Inhibition as Inflammatory Reset for PD Oligodendrocytes starts from the claim that modulating PDE4A, PDE4B, PDE4D within the disease context of neuroinflammation can redirect a disease-relevant process. The original description reads: "## Mechanistic Overview PDE4 Inhibition as Inflammatory Reset for PD Oligodendrocytes starts from the claim that The prosaposin-GPR37-IL-6 axis converges on cAMP signaling: GPR37 Gi-coupled signaling suppresses cAMP (pro-inflammatory) **Falsifiable Predictions:** 1. Pharmacological modulation of PDE4A will alter neuroinflammation 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:** $124,874 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.