Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.18 (overall 0.62) | 0.18 |
| cell type Human Protein Atlas | expressed broadly, no clear home in brain cells | 0.40 |
| chemistry Open Targets | compounds already reach it: me-344, metformin hydrochloride, metformin | 1.00 |
| trials ClinicalTrials.gov | 4 Parkinson's trials, 0 stopped | 1.00 |
| literature PubMed | 13 Parkinson's papers of 148 | 0.65 |
| pathways Reactome | 2 pathways; mostly mitochondrial quality control | 1.00 |
Knock down and overexpress NDUFV2 in a dopamine neuron, astrocyte and microglia tri-culture; measure PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub) and dopamine neuron survival after α-synuclein fibril challenge.
- Cell type
- a dopamine neuron, astrocyte and microglia tri-culture
- Direction
- Both arms: public data does not say which way helps; existing compounds already reach the inhibition arm.
- Molecular readout
- PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub)
- Functional readout
- dopamine neuron survival after α-synuclein fibril challenge
- Rule-out
- If neither arm moves PINK1–parkin mitophagy flux (mt-Keima) by 20% or more against non-targeting and empty-vector controls, across three independent differentiations, the hypothesis is wrong.
- Lab request
- CRISPRi knockdown and lentiviral overexpression of NDUFV2 in a tri-culture of iPSC dopamine neurons, astrocytes and microglia; n = 3 differentiations; readouts: PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub); dopamine neuron survival after α-synuclein fibril challenge. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Earlier readings: 2026-10-26 0.59; 2026-10-25 0.59; 2026-10-24 0.59; 2026-10-23 0.59.
Sealed predictions
- NDUFV2 in dopamine neurons, braak+0.15 (p 0.705) → +0.54 (p 0.130)receipt 0545
- NDUFV2 in dopamine neurons, braak+0.08 (p 0.597) → +0.07 (p 0.656)receipt 0063
- NDUFV2 in dopamine neurons, resilience-0.17 (p 1.000) → -0.66 (p 0.005)receipt 0064
Swarm cases
receipt 0545: NDUFV2 in dopamine neurons, braak
- power
- full sample +0.34 (p 0.161, n 18), 95% CI -0.15 to +0.70. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.32 (p 0.191, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.30 (p 0.232, n 18). could be the mix.
- skeptic
- leave-one-out range +0.24 to +0.44, sign flips 0; without severely affected donors +0.34 (p 0.161, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for NDUFV2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0064: NDUFV2 in dopamine neurons, resilience
- power
- full sample -0.55 (p 0.0048, n 55), 95% CI -0.71 to -0.34. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for age, sex and PMI: -0.52 (p 0.0085, n 55). holds up.
- composition
- dopamine neurons share of nuclei vs axis +0.12 (p 0.542); controlling for it: -0.52 (p 0.0085, n 55). not the mix.
- skeptic
- leave-one-out range -0.67 to -0.51, sign flips 0; without severely affected donors -0.56 (p 0.0056, n 46). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "differs in resilient donors (Lewy pathology, no parkinsonism)" for NDUFV2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0063: NDUFV2 in dopamine neurons, braak
- power
- full sample +0.06 (p 0.602, n 84), 95% CI -0.16 to +0.27. the interval sits on zero: probably nothing there.
- confounder
- adjusted for age, sex and PMI: +0.01 (p 0.900, n 84). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis -0.72 (p 1.8e-14); controlling for it: +0.02 (p 0.859, n 84). could be the mix.
- skeptic
- leave-one-out range +0.03 to +0.09, sign flips 0; without severely affected donors +0.04 (p 0.729, n 75). fragile.
- cell type
- strongest in oligodendrocytes: -0.49 (p 2.1e-6, n 84) vs +0.06 in dopamine neurons. proposing oligodendrocytes.
- axis
- resilience beats braak for NDUFV2 in dopamine neurons: -0.55 (p 0.0048, n 55). proposing resilience.
follow-up confirmed in ventral tegmental area.
follow-up NDUFV2 · oligodendrocytes · braak: ventral tegmental area -0.48 p 6.3e-6 (needs p < 0.0056)
follow-up NDUFV2 · dopamine neurons · resilience: ventral tegmental area +0.07 p 0.676 (needs p < 0.0050)
Receipts
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