Combinatorial Epigenetic Therapy Targeting REST Convergence Hub
Curated pathway from expert analysis
flowchart TD
A["REST/NRSF Transcriptional Repressor<br/>Neuronal Gene Silencing Factor"]
B["GABAergic and Synaptic Gene Suppression<br/>Non-neuronal Cell Identity Maintenance"]
C["Tau and ATXN2 Modulation<br/>Neurodegeneration Linkage"]
D["REST Deficiency in Aging<br/>Neurotoxic Gene Derepression"]
E["Neuronal Identity Loss<br/>Synaptic Vulnerability"]
F["REST Activating Compounds<br/>Neuroprotective Target Validation"]
G["AD and FTD Mechanisms<br/>REST-Dependent Protection Failure"]
A --> B
B --> C
C --> D
D --> E
E --> F
F --> G
style A fill:#7b1fa2,stroke:#ce93d8,color:#ce93d8
style E fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style F fill:#1b5e20,stroke:#81c784,color:#81c784No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for REST 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 REST pathway + combinatorial HDAC.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF 3-month-old 5xFAD mice receive 8-week intraperitoneal treatment with SAHA (10 mg/kg) + 5-aza-dC (0.5 mg/kg) thrice weekly, THEN spatial memory retention will improve by ≥25% in Morris water maze (l | ≥25% reduction in platform search latency during probe trial and ≥20% reduction in cortical Aβ42 ELISA levels versus vehicle. | — no observation — | pending | 0.55 |
| IF primary cortical neurons from a 5xFAD mouse model are treated for 7 days with combinatorial SAHA (1 µM) + 5-aza-2'-deoxycytidine (1 µM), THEN REST target gene expression (Bdnf exon IV, Ngn1, Syn1) | ≥30% upregulation of REST target genes by qRT-PCR with p<0.05, alongside maintained cell viability (>90% by Calcein-AM). | — no observation — | pending | 0.65 |