Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.60 from other evidence | 0.00 |
| cell type Human Protein Atlas | expressed broadly, no clear home in brain cells | 0.40 |
| chemistry Open Targets | compounds already reach it: metformin hydrochloride, me-344, metformin | 1.00 |
| trials ClinicalTrials.gov | 4 Parkinson's trials, 0 stopped | 1.00 |
| literature PubMed | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | 2 pathways; mostly mitochondrial quality control | 1.00 |
Knock down and overexpress NDUFS5 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 NDUFS5 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 0.61; 2026-10-25 0.61; 2026-10-24 0.61; 2026-10-23 0.61.
Sealed predictions
- NDUFS5 in dopamine neurons, braak+0.20 (p 0.615) → +0.31 (p 0.414)receipt 0557
- NDUFS5 in dopamine neurons, resilience+0.29 (p 0.358) → +0.43 (p 0.097)receipt 0082
- NDUFS5 in dopamine neurons, braak-0.16 (p 0.308) → +0.05 (p 0.740)receipt 0081
Swarm cases
receipt 0557: NDUFS5 in dopamine neurons, braak
- power
- full sample +0.19 (p 0.444, n 18), 95% CI -0.30 to +0.60. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.21 (p 0.398, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.29 (p 0.239, n 18). could be the mix.
- skeptic
- leave-one-out range +0.09 to +0.35, sign flips 0; without severely affected donors +0.19 (p 0.444, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for NDUFS5 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0082: NDUFS5 in dopamine neurons, resilience
- power
- full sample +0.37 (p 0.061, n 55), 95% CI +0.11 to +0.58. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for age, sex and PMI: +0.41 (p 0.037, n 55). holds up.
- composition
- dopamine neurons share of nuclei vs axis +0.12 (p 0.542); controlling for it: +0.42 (p 0.034, n 55). not the mix.
- skeptic
- leave-one-out range +0.32 to +0.50, sign flips 0; without severely affected donors +0.39 (p 0.052, n 46). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "differs in resilient donors (Lewy pathology, no parkinsonism)" for NDUFS5 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0081: NDUFS5 in dopamine neurons, braak
- power
- full sample -0.02 (p 0.838, n 84), 95% CI -0.24 to +0.19. the interval sits on zero: probably nothing there.
- confounder
- adjusted for age, sex and PMI: -0.06 (p 0.573, n 84). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis -0.72 (p 1.8e-14); controlling for it: -0.10 (p 0.370, n 84). could be the mix.
- skeptic
- leave-one-out range -0.05 to +0.00, sign flips 1; without severely affected donors -0.03 (p 0.768, n 75). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for NDUFS5 in dopamine neurons.
case closed: nothing better to follow up.
Receipts
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