Migratory animals maintain spatial memories across generations through epigenetic modifications. Reactivating these pathways could restore lost spatial memories in Alzheimer's patients by reinstating dormant memory traces.
Auto-built from this analysis's top knowledge-graph edges.
graph TD
AMPK["AMPK"] -->|regulates| mitochondrial_biogenesis["mitochondrial_biogenesis"]
PGC_1_["PGC-1α"] -->|activates| oxidative_metabolism["oxidative_metabolism"]
BDNF["BDNF"] -->|enhances| synaptic_plasticity["synaptic_plasticity"]
BDNF_1["BDNF"] -->|activates| memory_formation["memory formation"]
Glucocorticoid_receptor["Glucocorticoid receptor"] -->|regulates| Stress_response["Stress response"]
CLOCK["CLOCK"] -->|regulates| Circadian_rhythm["Circadian rhythm"]
BMAL1["BMAL1"] -->|regulates| Circadian_rhythm_2["Circadian rhythm"]
DNMT3A["DNMT3A"] -->|regulates| EPIGENETIC_MODIFICATION["EPIGENETIC MODIFICATION"]
n5_azacytidine["5-azacytidine"] -.->|inhibits| DNMT3A_3["DNMT3A"]
Decitabine["Decitabine"] -.->|inhibits| DNMT3A_4["DNMT3A"]
hippocampal_place_cells["hippocampal_place_cells"] -->|regulates| spatial_memory["spatial memory"]
FKBP5["FKBP5"] -->|modulates| glucocorticoid_signaling["glucocorticoid_signaling"]
style AMPK fill:#ce93d8,stroke:#333,color:#000
style mitochondrial_biogenesis fill:#81c784,stroke:#333,color:#000
style PGC_1_ fill:#ce93d8,stroke:#333,color:#000
style oxidative_metabolism fill:#81c784,stroke:#333,color:#000
style BDNF fill:#ce93d8,stroke:#333,color:#000
style synaptic_plasticity fill:#81c784,stroke:#333,color:#000
style BDNF_1 fill:#ce93d8,stroke:#333,color:#000
style memory_formation fill:#4fc3f7,stroke:#333,color:#000
style Glucocorticoid_receptor fill:#4fc3f7,stroke:#333,color:#000
style Stress_response fill:#4fc3f7,stroke:#333,color:#000
style CLOCK fill:#ce93d8,stroke:#333,color:#000
style Circadian_rhythm fill:#81c784,stroke:#333,color:#000
style BMAL1 fill:#ce93d8,stroke:#333,color:#000
style Circadian_rhythm_2 fill:#81c784,stroke:#333,color:#000
style DNMT3A fill:#ce93d8,stroke:#333,color:#000
style EPIGENETIC_MODIFICATION fill:#4fc3f7,stroke:#333,color:#000
style n5_azacytidine fill:#4fc3f7,stroke:#333,color:#000
style DNMT3A_3 fill:#ce93d8,stroke:#333,color:#000
style Decitabine fill:#4fc3f7,stroke:#333,color:#000
style DNMT3A_4 fill:#ce93d8,stroke:#333,color:#000
style hippocampal_place_cells fill:#4fc3f7,stroke:#333,color:#000
style spatial_memory fill:#4fc3f7,stroke:#333,color:#000
style FKBP5 fill:#ce93d8,stroke:#333,color:#000
style glucocorticoid_signaling fill:#81c784,stroke:#333,color:#000No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for DNMT3A 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 DNMT3A, CREB-binding protein (CBP).
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF CBP is pharmacologically activated in the entorhinal cortex of APP/PS1 mice using a CBP-activating small molecule (CC-10175031, 10mg/kg/day i.p. for 3 weeks), THEN place cell stability and spatial | 30% increase in place cell stability (spatial information content) and grid cell spatial coherence scores | — no observation — | pending | 0.45 |
| IF DNMT3A is selectively overexpressed in the dorsal hippocampus of 5xFAD transgenic mice via bilateral AAV-mediated gene delivery at 6 months of age, THEN these mice will demonstrate a ≥25% improveme | 25% improvement in spatial memory retention (time in target quadrant during probe trial) | — no observation — | pending | 0.55 |