Pharmacological FABP inhibition (BMS-309403) or siRNA targeting FABP5/7 interrupts intercellular lipid transfer between neurons and microglia. Pathway-proximal intervention that addresses the lipid relay mechanism directly. Plausible therapeutic hedge requiring cell-type-specific validation and construct deconvolution to address redundancy concerns.
Curated pathway from expert analysis
flowchart TD
A["FABP5/FABP7 (fatty acid binding proteins)<br/>Primary Target"]
B["Biological Process 1<br/>Mechanistic Step A"]
C["Biological Process 2<br/>Mechanistic Step B"]
D["Output Phenotype<br/>Disease Effect"]
A --> B
B --> C
C --> D
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style D fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9aNo linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for FABP5 yet. Search RCSB →
Median TPM across 13 brain regions for FABP5/FABP7 (fatty acid binding proteins) from GTEx v10.
No clinical trials data linked to this hypothesis yet.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for FABP5.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF human iPSC‑derived neuron‑microglia co‑cultures are transfected with 50 nM siRNA targeting FABP5 and FABP7 for 48 h, THEN intercellular lipid transfer, measured by BODIPY‑C12 fatty‑acid analog tran | ≥40 % decrease in BODIPY‑C12 fluorescence signal in microglia after FABP5/7 knockdown. | — no observation — | pending | 0.60 |
| IF adult 5xFAD mice are treated with oral BMS-309403 (30 mg/kg, once daily) for 8 weeks, THEN hippocampal microglial lipid droplet density will be reduced by ≥30 % relative to vehicle‑treated controls | At least a 30 % decrease in microglial lipid droplet count per hippocampal region after 8 weeks of BMS‑309403. | — no observation — | pending | 0.55 |