Selective GluN2A activation or GluN2B inhibition shifts balance from excitotoxic extrasynaptic signaling toward neuroprotective synaptic signaling. Deprioritized due to memantine's modest clinical efficacy and technical challenges in confirming in vivo compartmentalization.
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 curated PDB or AlphaFold mapping for GRIN2A 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 GRIN2A.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.