symbol,module,role,target_to_intervention_score_100,tractability_class,model,primary_assay,chembl_target_id,pdb_count,alphafold_url,recommended_next_experiment
SNCA,alpha-synuclein aggregation and propagation,central PD pathology target,97.0,highest-priority intervention target,SNCA triplication/A53T iPSC dopaminergic neurons or alpha-synuclein PFF model,"pS129 alpha-synuclein, aggregate load, synaptic/neurite phenotypes",CHEMBL6152,165,https://alphafold.ebi.ac.uk/entry/P37840,"Use alpha-synuclein PFF or SNCA-mutant iPSC dopaminergic neurons with pS129 aggregation, synaptic, and viability endpoints."
GLP1R,metabolic and GLP-1 receptor signalling,repurposing target with phase 2 PD signals,94.0,highest-priority intervention target,dopaminergic neuron stress model with metabolic/inflammatory co-culture,"neuronal survival, inflammatory cytokines, mitochondrial respiration",CHEMBL1784,56,https://alphafold.ebi.ac.uk/entry/P43220,"Test GLP-1 agonists in metabolic/inflammatory stress co-culture with neuronal survival, cytokines, and mitochondrial respiration endpoints."
LRRK2,LRRK2 kinase and lysosomal stress,genetically anchored kinase target,90.0,highest-priority intervention target,LRRK2 G2019S or R1441C iPSC-derived dopaminergic neurons,"phospho-Rab10/Rab12, lysosomal morphology, neurite survival",CHEMBL1075104,0,https://alphafold.ebi.ac.uk/entry/A0A7P0Z4D9,"Test best-supported LRRK2 inhibitors in G2019S iPSC dopaminergic neurons using phospho-Rab10, lysosome, mitochondrial, and neurite endpoints."
GBA1,GBA1 lysosome/autophagy,lysosomal enzyme and PD risk gene,90.0,highest-priority intervention target,GBA1-mutant iPSC dopaminergic neurons and macrophage/microglia-like cells,"glucocerebrosidase activity, lysosomal pH, alpha-synuclein burden",CHEMBL2179,0,https://alphafold.ebi.ac.uk/entry/A0A0G2JLB3,"Test GCase modulators in GBA1-mutant iPSC dopaminergic neurons using GCase activity, lysosomal pH, alpha-synuclein, and survival endpoints."
SLC6A3,dopaminergic synapse,dopamine transporter marker and dopaminergic phenotype readout,88.0,highest-priority intervention target,iPSC dopaminergic neuron maturation/readout assay,"DAT expression/function, dopamine uptake, neuron identity QC",CHEMBL238,7,https://alphafold.ebi.ac.uk/entry/Q01959,"Run target-specific perturbation in iPSC dopaminergic neuron maturation/readout assay using DAT expression/function, dopamine uptake, neuron identity QC."
TLR2,innate immune signalling,Reactome-highlighted innate immune receptor,85.6,highest-priority intervention target,iPSC-derived microglia and neuron-microglia co-culture,"TNF/IL6/IL1B release, NF-kB activation, neuronal toxicity",CHEMBL3301399,7,https://alphafold.ebi.ac.uk/entry/O60603,"Validate immune modulation in iPSC-derived microglia/neuron co-culture using cytokines, NF-kB/stress markers, and neuronal toxicity."
IL17A,IL-17 inflammatory signalling,Reactome-highlighted cytokine pathway node,82.0,highest-priority intervention target,microglia/astrocyte inflammatory co-culture,"IL-17 response genes, cytokine release, neuronal stress markers",CHEMBL3390822,36,https://alphafold.ebi.ac.uk/entry/Q16552,"Validate immune modulation in iPSC-derived microglia/neuron co-culture using cytokines, NF-kB/stress markers, and neuronal toxicity."
PINK1,mitochondrial quality control,mitophagy kinase and recessive PD gene,78.7,highest-priority intervention target,PINK1 knockout iPSC dopaminergic neurons,"mitophagy reporter, mitochondrial membrane potential, ATP/ROS",CHEMBL3337330,3,https://alphafold.ebi.ac.uk/entry/Q9BXM7,Use iPSC dopaminergic neurons with mitochondrial stress and mitophagy/respiration/ROS assays.
NTRK1,NTRK/neurotrophin signalling,Reactome-highlighted trophic signalling node,78.0,highest-priority intervention target,dopaminergic neuron survival/trophic support model,"neurite length, survival, phospho-ERK/AKT",CHEMBL2815,0,https://alphafold.ebi.ac.uk/entry/A0A6Q8PF65,"Run target-specific perturbation in dopaminergic neuron survival/trophic support model using neurite length, survival, phospho-ERK/AKT."
MAPK1,MAP kinase activation,Reactome-highlighted signalling hub,78.0,highest-priority intervention target,stress-response assay in neurons and microglia,"phospho-ERK, inflammatory/stress response, toxicity counterscreen",CHEMBL4040,0,https://alphafold.ebi.ac.uk/entry/Q499G7,"Run target-specific perturbation in stress-response assay in neurons and microglia using phospho-ERK, inflammatory/stress response, toxicity counterscreen."
NOD2,NOD1/2 inflammatory signalling,Reactome-highlighted innate immune sensor,75.0,strong validation target,iPSC-derived microglia or monocyte-derived macrophages,"NOD ligand response, cytokines, inflammasome-related markers",CHEMBL1293266,0,https://alphafold.ebi.ac.uk/entry/A0A3S6A229,"Validate immune modulation in iPSC-derived microglia/neuron co-culture using cytokines, NF-kB/stress markers, and neuronal toxicity."
NDUFS3,mitochondrial oxidative phosphorylation,complex I pathway marker from pilot omics,66.5,strong validation target,iPSC dopaminergic neuron mitochondrial stress model,"Seahorse OCR, complex I activity, ATP/ROS",CHEMBL6067008,0,https://alphafold.ebi.ac.uk/entry/E9PS48,Use iPSC dopaminergic neurons with mitochondrial stress and mitophagy/respiration/ROS assays.
LAMP2,lysosome/autophagy,lysosomal/autophagy marker,66.5,strong validation target,iPSC dopaminergic neurons with lysosomal stress,"LC3/p62 flux, lysosomal pH, autophagosome clearance",CHEMBL5465542,0,https://alphafold.ebi.ac.uk/entry/A0A9L9PXQ4,"Run target-specific perturbation in iPSC dopaminergic neurons with lysosomal stress using LC3/p62 flux, lysosomal pH, autophagosome clearance."
MYD88,innate immune signalling,TLR adaptor in Reactome MyD88/MAL cascade,64.2,strong validation target,iPSC-derived microglia inflammatory challenge,"NF-kB reporter, cytokine release, rescue of co-culture toxicity",CHEMBL5919,0,https://alphafold.ebi.ac.uk/entry/A0A0A0MSI9,"Validate immune modulation in iPSC-derived microglia/neuron co-culture using cytokines, NF-kB/stress markers, and neuronal toxicity."
PRKN,mitochondrial quality control,E3 ligase and recessive PD gene,64.0,strong validation target,PRKN knockout iPSC dopaminergic neurons,"mitophagy reporter, ubiquitination, mitochondrial stress survival",,0,https://alphafold.ebi.ac.uk/entry/A0A669KBE3,Use iPSC dopaminergic neurons with mitochondrial stress and mitophagy/respiration/ROS assays.