Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.12 (overall 0.09) | 0.12 |
| cell type Human Protein Atlas | expressed broadly, no clear home in brain cells | 0.40 |
| 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 | 1 Parkinson's papers of 197 | 0.91 |
| pathways Reactome | 1 pathway; mostly lysosome and autophagy | 1.00 |
Knock down and overexpress CERS6 in a dopamine neuron, astrocyte and microglia tri-culture; measure glucocerebrosidase (GCase) activity and LC3-II and p62 flux and dopamine neuron survival after α-synuclein fibril challenge.
- Cell type
- a dopamine neuron, astrocyte and microglia tri-culture
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- glucocerebrosidase (GCase) activity and LC3-II and p62 flux
- Functional readout
- dopamine neuron survival after α-synuclein fibril challenge
- Rule-out
- If neither arm moves glucocerebrosidase (GCase) activity 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 CERS6 in a tri-culture of iPSC dopamine neurons, astrocytes and microglia; n = 3 differentiations; readouts: glucocerebrosidase (GCase) activity and LC3-II and p62 flux; dopamine neuron survival after α-synuclein fibril challenge. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- CERS6 in dopamine neurons, braak-0.18 (p 0.635) → -0.28 (p 0.466)receipt 2919
Swarm cases
receipt 2919: CERS6 in dopamine neurons, braak
- power
- full sample -0.14 (p 0.591, n 18), 95% CI -0.57 to +0.35. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.09 (p 0.735, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.07 (p 0.774, n 18). could be the mix.
- skeptic
- leave-one-out range -0.27 to -0.03, sign flips 0; without severely affected donors -0.14 (p 0.591, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CERS6 in dopamine neurons.
case closed: nothing better to follow up.
Receipts
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