BET Bromodomain Inhibition for Neuroinflammation Suppression
Curated pathway from expert analysis
flowchart TD
A["BRD4 Reader<br/>Bromo and ET Domains"]
B["Acetyl-Lysine Recognition<br/>Histone Tail Binding"]
C["P-TEFb Release<br/>CDK9 Cyclin T1 Activation"]
D["RNA Pol II Elongation<br/>Super-Enhancer Targets"]
E["c-MYC Upregulation<br/>Proliferative Gene Expression"]
F["NFKB Pathway<br/>Pro-inflammatory Transcriptional Program"]
G["BRD4 Inhibition<br/>JQ1 or OTX015 Treatment"]
H["Anti-inflammatory Effect<br/>Pro-survival Gene Suppression"]
I["Tau Pathology<br/>Kinase Regulation"]
J["Neuronal Death<br/>BRD4-Driven Vulnerability"]
A --> B
B --> C
C --> D
D --> E
D --> F
F --> H
G --> H
G -.->|"reduces"| E
F --> I
I --> J
style A fill:#7b1fa2,stroke:#ce93d8,color:#ce93d8
style J fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9aNo linked papers recorded for this hypothesis yet.
Median TPM across 13 brain regions for BRD4 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 BRD4.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF iPSC-derived microglia from sporadic Alzheimer's disease patients are treated with JQ1 (500 nM) for 48 hours following LPS stimulation (100 ng/mL), THEN secreted IL-6 and CXCL10 concentrations in c | ≥50% reduction in IL-6 and CXCL10 secretion from JQ1-treated microglia | — no observation — | pending | 0.48 |
| IF C57BL/6 mice receive daily intraperitoneal JQ1 (50 mg/kg) starting 24 hours after MPTP injection for 21 days, THEN striatal TNF-α and IL-1β protein levels will decrease by ≥40% compared to vehicle- | ≥40% reduction in striatal pro-inflammatory cytokines (TNF-α, IL-1β) with JQ1 treatment | — no observation — | pending | 0.55 |