Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.09 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocyte progenitor cells; strongest in bergmann glia | 0.75 |
| chemistry Open Targets | compounds already reach it: xl-418, mk-2206, uprosertib +10 | 0.90 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 8 Parkinson's papers of 1,233 | 0.71 |
| pathways Reactome | 29 pathways; mostly mitochondrial quality control | 1.00 |
Knock down and overexpress AKT3 in oligodendrocytes; measure PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub) and α-synuclein uptake and myelin basic protein output under oxidative stress.
- Cell type
- oligodendrocytes
- 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
- α-synuclein uptake and myelin basic protein output under oxidative stress
- 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 AKT3 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub); α-synuclein uptake and myelin basic protein output under oxidative stress. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- AKT3 in oligodendrocytes, braak+0.11 (p 0.773) → -0.05 (p 0.891)receipt 2961
- AKT3 in dopamine neurons, braak+0.41 (p 0.272) → -0.33 (p 0.389)receipt 2962
Swarm cases
receipt 2962: AKT3 in dopamine neurons, braak
- power
- full sample +0.04 (p 0.867, n 18), 95% CI -0.43 to +0.50. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.05 (p 0.834, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.08 (p 0.767, n 18). could be the mix.
- skeptic
- leave-one-out range -0.07 to +0.17, sign flips 4; without severely affected donors +0.04 (p 0.867, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for AKT3 in dopamine neurons.
case closed: nothing better to follow up.
receipt 2961: AKT3 in oligodendrocytes, braak
- power
- full sample +0.07 (p 0.787, n 18), 95% CI -0.41 to +0.52. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.05 (p 0.834, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.03 (p 0.922, n 18). could be the mix.
- skeptic
- leave-one-out range -0.06 to +0.20, sign flips 2; without severely affected donors +0.07 (p 0.787, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for AKT3 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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