Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.02 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in microglia (3037 nCPM) | 1.00 |
| chemistry Open Targets | a small-molecule pocket | 0.60 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 3 Parkinson's papers of 695 | 0.82 |
| pathways Reactome | 2 pathways; mostly growth signalling | 0.60 |
Knock down and overexpress MEF2A in microglia; measure phospho-ERK and phospho-AKT response to GDNF and uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release).
- Cell type
- microglia
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- phospho-ERK and phospho-AKT response to GDNF
- Functional readout
- uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release)
- Rule-out
- If neither arm moves phospho-ERK 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 MEF2A in iPSC-derived microglia (iMGL); n = 3 differentiations; readouts: phospho-ERK and phospho-AKT response to GDNF; uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release). Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- MEF2A in dopamine neurons, braak-0.16 (p 0.685) → +0.35 (p 0.354)receipt 7341
- MEF2A in microglia, braak+0.09 (p 0.821) → +0.25 (p 0.523)receipt 7340
Swarm cases
receipt 7341: MEF2A in dopamine neurons, braak
- power
- full sample +0.11 (p 0.658, n 18), 95% CI -0.37 to +0.55. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.11 (p 0.664, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.09 (p 0.715, n 18). could be the mix.
- skeptic
- leave-one-out range +0.02 to +0.29, sign flips 0; without severely affected donors +0.11 (p 0.658, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for MEF2A in dopamine neurons.
case closed: nothing better to follow up.
receipt 7340: MEF2A in microglia, braak
- power
- full sample +0.17 (p 0.498, n 18), 95% CI -0.32 to +0.59. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.22 (p 0.379, n 18). does not hold up.
- composition
- microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: +0.18 (p 0.471, n 18). could be the mix.
- skeptic
- leave-one-out range +0.07 to +0.30, sign flips 0; without severely affected donors +0.17 (p 0.498, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for MEF2A in microglia.
case closed: nothing better to follow up.
Receipts
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