Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.23 (overall 0.15) | 0.23 |
| cell type Human Protein Atlas | expressed broadly, no clear home in brain cells | 0.40 |
| chemistry Open Targets | compounds already reach it: selonsertib | 0.90 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 2 Parkinson's papers of 185 | 0.85 |
| pathways Reactome | 1 pathway; mostly iron and oxidative stress | 0.80 |
Knock down and overexpress MAP3K5 in a dopamine neuron, astrocyte and microglia tri-culture; measure reactive oxygen species (CellROX) and lipid peroxidation and labile iron 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
- reactive oxygen species (CellROX) and lipid peroxidation and labile iron
- Functional readout
- dopamine neuron survival after α-synuclein fibril challenge
- Rule-out
- If neither arm moves reactive oxygen species (CellROX) 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 MAP3K5 in a tri-culture of iPSC dopamine neurons, astrocytes and microglia; n = 3 differentiations; readouts: reactive oxygen species (CellROX) and lipid peroxidation and labile iron; dopamine neuron survival after α-synuclein fibril challenge. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- MAP3K5 in dopamine neurons, braak-0.16 (p 0.672) → -0.44 (p 0.240)receipt 2184
Swarm cases
receipt 2184: MAP3K5 in dopamine neurons, braak
- power
- full sample -0.33 (p 0.179, n 18), 95% CI -0.69 to +0.16. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.34 (p 0.164, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.32 (p 0.194, n 18). could be the mix.
- skeptic
- leave-one-out range -0.49 to -0.25, sign flips 0; without severely affected donors -0.33 (p 0.179, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for MAP3K5 in dopamine neurons.
case closed: nothing better to follow up.
Receipts
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