Braak stage 1, 100% of pigmented neurons left
parkinsonconnecting

Gene record

BCL2L1

BCL2 like 1

translation score 0.57, read 2026-10-18; 1 sealed predictions, 0 held; 1 receipts.

Six readers

readerfoundscore
genetics
Open Targets		genetic association 0.17 (overall 0.11)0.17
cell type
Human Protein Atlas		expressed broadly, no clear home in brain cells0.40
chemistry
Open Targets		compounds already reach it: obatoclax, navitoclax, obatoclax mesylate0.90
trials
ClinicalTrials.gov		no Parkinson's trials on record: an open field1.00
literature
PubMed		12 Parkinson's papers of 9020.66
pathways
Reactome		7 pathways; mostly immune signalling0.90
proposal for BCL2L1, translation score 0.57

Knock down and overexpress BCL2L1 in a dopamine neuron, astrocyte and microglia tri-culture; measure IL-1β and TNF release and surface HLA-DR 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; existing compounds already reach the inhibition arm.
Molecular readout
IL-1β and TNF release and surface HLA-DR
Functional readout
dopamine neuron survival after α-synuclein fibril challenge
Rule-out
If neither arm moves IL-1β 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 BCL2L1 in a tri-culture of iPSC dopamine neurons, astrocytes and microglia; n = 3 differentiations; readouts: IL-1β and TNF release and surface HLA-DR; 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

  1. BCL2L1 in dopamine neurons, braak-0.13 (p 0.735) → -0.21 (p 0.586)receipt 2522

Swarm cases

receipt 2522: BCL2L1 in dopamine neurons, braak

power
full sample -0.21 (p 0.398, n 18), 95% CI -0.62 to +0.28. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: -0.27 (p 0.277, 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 -0.36 to -0.11, sign flips 0; without severely affected donors -0.21 (p 0.398, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for BCL2L1 in dopamine neurons.

case closed: nothing better to follow up.

Receipts

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