Synthetic REV-ERB agonists to directly suppress microglial activation markers through circadian nuclear receptor signaling, bypassing sleep-dependent mechanisms
Curated pathway from expert analysis
flowchart TD
A["Microglial Chronic Activation<br/>AD Neuroinflammatory State"]
B["Circadian Clock Dysregulation<br/>BMAL1 CLOCK Disrupted"]
C["REV-ERB Alpha NR1D1<br/>Nuclear Receptor Expressed in Microglia"]
D["Synthetic REV-ERB Agonist<br/>SR9009 SR9011 Treatment"]
E["NR1D1 NR1D2 Activation<br/>Transcriptional Repressor Function"]
F["IL-6 TNF-alpha NLRP3 Suppressed<br/>Inflammatory Gene Repression"]
G["Microglial Deactivation<br/>DAM to Homeostatic Transition"]
H["Neuroprotection<br/>Amyloid and Tau Pathology Reduced"]
A --> B
B --> C
C --> D
D --> E
E --> F
F --> G
G --> H
style E fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style H fill:#1b5e20,stroke:#a5d6a7,color:#a5d6a7No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for NR1D1 yet. Search RCSB →
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 NR1D1.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.