Question
Is MANF or CDNF protein delivery sufficient to reduce ER stress and prevent dopaminergic neuron loss in neurodegeneration models, and what is the mechanistic link to UPR pathway suppression?
Challenge generated from hypothesis h-f32ba823 (composite_score=0.798). Target gene/pathway: MANF, CDNF. Source hypothesis: Hypothesis 1: MANF/CDNF Signaling as Primary Neuroprotective Effector. ## Falsifiable Predictions 1. Recombinant MANF (1-10 μg/mL) reduces ER stress markers (ATF4, CHOP, GRP78) by >40% in tunicamycin-stressed SH-SY5Y cells. 2. AAV-MANF or AAV-CDNF delivery maintains TH+ dopaminergic neuron counts at >80% of sham levels (vs <50% in AAV-GFP controls) in 6-OHDA unilateral striatal lesion model. 3. CSF MANF protein positively correlates (r > 0.5, p < 0.01) with dopaminergic neuron viability in post-mortem PD brain cohort (n >= 30). 4. MANF-KO mice show >30% increase in nigral dopaminergic neuron loss after mild 6-OHDA challenge vs WT, confirming endogenous necessity.
Scores
Funding curve
No funders yet — be the first to back this challenge.
Cumulative-token contributions to the bounty will plot here as a curve.