Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.24 (overall 0.17) | 0.24 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocyte progenitor cells; strongest in proximal tubule cells | 0.75 |
| chemistry Open Targets | hard to drug | 0.00 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 6 Parkinson's papers of 157 | 0.74 |
| pathways Reactome | 2 pathways; mostly mitochondrial quality control | 1.00 |
Knock down and overexpress GLUD2 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.
- 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 GLUD2 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
- GLUD2 in oligodendrocytes, braak-0.05 (p 0.892) → +0.07 (p 0.859)receipt 2152
- GLUD2 in dopamine neurons, braak-0.29 (p 0.457) → +0.66 (p 0.051)receipt 2153
Swarm cases
receipt 2153: GLUD2 in dopamine neurons, braak
- power
- full sample +0.09 (p 0.735, n 18), 95% CI -0.40 to +0.53. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.18 (p 0.471, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.18 (p 0.482, n 18). could be the mix.
- skeptic
- leave-one-out range -0.03 to +0.22, sign flips 2; without severely affected donors +0.09 (p 0.735, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GLUD2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 2152: GLUD2 in oligodendrocytes, braak
- power
- full sample +0.22 (p 0.374, n 18), 95% CI -0.27 to +0.62. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.33 (p 0.185, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.27 (p 0.281, n 18). could be the mix.
- skeptic
- leave-one-out range +0.11 to +0.40, sign flips 0; without severely affected donors +0.22 (p 0.374, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GLUD2 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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