Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.04 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in astrocytes (574 nCPM) | 1.00 |
| chemistry Open Targets | hard to drug | 0.40 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 5 Parkinson's papers of 543 | 0.76 |
| pathways Reactome | 3 pathways; mostly mitochondrial quality control | 1.00 |
Knock down and overexpress GLUD1 in astrocytes; measure PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub) and α-synuclein uptake and degradation, and dopamine neuron survival in co-culture.
- Cell type
- astrocytes
- 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 degradation, and dopamine neuron survival in co-culture
- 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 GLUD1 in iPSC-derived midbrain astrocytes; n = 3 differentiations; readouts: PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub); α-synuclein uptake and degradation, and dopamine neuron survival in co-culture. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- GLUD1 in dopamine neurons, braak+0.02 (p 0.962) → -0.33 (p 0.387)receipt 6046
- GLUD1 in astrocytes, braak-0.76 (p 0.016) → +0.05 (p 0.893)receipt 6045
Swarm cases
receipt 6046: GLUD1 in dopamine neurons, braak
- power
- full sample -0.11 (p 0.652, n 18), 95% CI -0.55 to +0.37. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.20 (p 0.429, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.03 (p 0.922, n 18). could be the mix.
- skeptic
- leave-one-out range -0.26 to -0.02, sign flips 0; without severely affected donors -0.11 (p 0.652, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GLUD1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 6045: GLUD1 in astrocytes, braak
- power
- full sample -0.48 (p 0.045, n 18), 95% CI -0.77 to -0.01. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for sex: -0.47 (p 0.050, n 18). holds up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: -0.26 (p 0.298, n 18). could be the mix.
- skeptic
- leave-one-out range -0.66 to -0.42, sign flips 0; without severely affected donors -0.48 (p 0.045, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GLUD1 in astrocytes.
case closed: nothing better to follow up.
Receipts
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