SIRT1 activation promotes mitophagy via PINK1/Parkin, reduces oxidative stress, and decreases DPR levels in cellular models. Marginally feasible given resveratrol's failure in AD trials, but warrants testing with selective activators in C9-specific models.
Auto-built from this analysis's top knowledge-graph edges.
graph TD
NRF2["NRF2"] -->|regulates| ARE_gene_transcription["ARE gene transcription"]
NFE2L2["NFE2L2"] -->|regulates| ARE_gene_transcription_1["ARE gene transcription"]
NRF2_activation["NRF2 activation"] -->|protective against| neurodegenerative_disease["neurodegenerative diseases"]
NRF2_nuclear_localization["NRF2 nuclear localization"] -->|biomarker for| Alzheimer_s_disease["Alzheimer's disease"]
NQO1["NQO1"] -->|regulates| redox_homeostasis["redox homeostasis"]
HO_1["HO-1"] -->|regulates| redox_homeostasis_2["redox homeostasis"]
TREM2["TREM2"] -->|regulates| microglial_metabolic_repr["microglial metabolic reprogramming"]
TREM2_deficiency["TREM2 deficiency"] -->|causes| impaired_amyloid_plaque_e["impaired amyloid plaque enclosure"]
TREM2_agonism["TREM2 agonism"] -->|protective against| amyloid_associated_neurot["amyloid-associated neurotoxicity"]
neuronal_activity["neuronal activity"] -->|regulates| tau_propagation["tau propagation"]
CDK5["CDK5"] -->|regulates| tau_packaging_into_exosom["tau packaging into exosomes"]
NLRP3_inflammasome_activa["NLRP3 inflammasome activation"] -->|causes| IL_1__release["IL-1β release"]
style NRF2 fill:#ce93d8,stroke:#333,color:#000
style ARE_gene_transcription fill:#81c784,stroke:#333,color:#000
style NFE2L2 fill:#ce93d8,stroke:#333,color:#000
style ARE_gene_transcription_1 fill:#4fc3f7,stroke:#333,color:#000
style NRF2_activation fill:#4fc3f7,stroke:#333,color:#000
style neurodegenerative_disease fill:#ef5350,stroke:#333,color:#000
style NRF2_nuclear_localization fill:#4fc3f7,stroke:#333,color:#000
style Alzheimer_s_disease fill:#ef5350,stroke:#333,color:#000
style NQO1 fill:#4fc3f7,stroke:#333,color:#000
style redox_homeostasis fill:#4fc3f7,stroke:#333,color:#000
style HO_1 fill:#4fc3f7,stroke:#333,color:#000
style redox_homeostasis_2 fill:#4fc3f7,stroke:#333,color:#000
style TREM2 fill:#4fc3f7,stroke:#333,color:#000
style microglial_metabolic_repr fill:#4fc3f7,stroke:#333,color:#000
style TREM2_deficiency fill:#4fc3f7,stroke:#333,color:#000
style impaired_amyloid_plaque_e fill:#4fc3f7,stroke:#333,color:#000
style TREM2_agonism fill:#4fc3f7,stroke:#333,color:#000
style amyloid_associated_neurot fill:#4fc3f7,stroke:#333,color:#000
style neuronal_activity fill:#4fc3f7,stroke:#333,color:#000
style tau_propagation fill:#4fc3f7,stroke:#333,color:#000
style CDK5 fill:#4fc3f7,stroke:#333,color:#000
style tau_packaging_into_exosom fill:#4fc3f7,stroke:#333,color:#000
style NLRP3_inflammasome_activa fill:#4fc3f7,stroke:#333,color:#000
style IL_1__release fill:#4fc3f7,stroke:#333,color:#000No linked papers recorded for this hypothesis yet.
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 SIRT1.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.