Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.08 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocytes; strongest in plasma cells | 0.75 |
| chemistry Open Targets | a small-molecule pocket | 0.60 |
| trials ClinicalTrials.gov | 1 Parkinson's trial, 0 stopped | 1.00 |
| literature PubMed | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | 4 pathways; mostly vesicle traffic | 1.00 |
Knock down and overexpress BGLAP in oligodendrocytes; measure LRRK2 kinase activity (pT73-Rab10) and lysosome position 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
- LRRK2 kinase activity (pT73-Rab10) and lysosome position
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves LRRK2 kinase activity (pT73-Rab10) 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 BGLAP in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: LRRK2 kinase activity (pT73-Rab10) and lysosome position; 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
- BGLAP in dopamine neurons, braakn/a → n/areceipt 3274
- BGLAP in oligodendrocytes, braakn/a → n/areceipt 3273
Swarm cases
receipt 3274: BGLAP in dopamine neurons, braak
- cell type
- BGLAP is not measured in dopamine neurons; looking elsewhere.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for BGLAP in dopamine neurons.
case closed: nothing better to follow up.
receipt 3273: BGLAP in oligodendrocytes, braak
- cell type
- BGLAP is not measured in oligodendrocytes; looking elsewhere.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for BGLAP in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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