Co-targeting CHRNA7 and LDLR to restore spatial cross-talk between cholinergic signaling and membrane domains disrupted in AD
Debate provenance: derived from debate `sess_SDA-2026-04-01-gap-lipid-rafts-2026-04-01` on question: Investigate how lipid raft composition (cholesterol metabolism, sphingolipids) changes in synaptic membranes during neurodegeneration and their mechanistic role in amyloid-beta processing and synapse dysfunction. Consensus signal: clinical_trialist, domain_expert, synthesizer, theorist discussed the mechanism terms CHRNA7, Co-Modulators, LDLR, Nicotinic, Receptor-Lipid, signaling. Novelty signal: synthesizer-consensus.
Auto-built from this analysis's top knowledge-graph edges.
graph TD
ASM["ASM"] -->|activates| Ceramide["Ceramide"]
SMPD1_mutations["SMPD1 mutations"] -->|causes| Niemann_Pick_disease_type["Niemann-Pick disease type A"]
SMPD1_mutations_1["SMPD1 mutations"] -->|causes| Neurodegeneration["Neurodegeneration"]
Ceramide_2["Ceramide"] -->|regulates| Apoptosis["Apoptosis"]
Amitriptyline["Amitriptyline"] -.->|inhibits| ASM_3["ASM"]
SREBF2_dysregulation["SREBF2 dysregulation"] -->|alters| de_novo_cholesterol_synth["de novo cholesterol synthesis"]
ABCA1["ABCA1"] -->|modulates| cholesterol_efflux["cholesterol efflux"]
Ceramide_accumulation["Ceramide accumulation"] -->|causes| Lysosomal_membrane_permea["Lysosomal membrane permeabilization"]
Acid_sphingomyelinase["Acid sphingomyelinase"] -->|causes| Lysosomal_destabilization["Lysosomal destabilization"]
UNC1062["UNC1062"] -.->|inhibits| ASM_4["ASM"]
Lysosomal_membrane_permea_5["Lysosomal membrane permeabilization"] -->|causes| Cathepsin_release["Cathepsin release"]
Selective_ASM_inhibitors["Selective ASM inhibitors"] -->|therapeutic target| Neuroprotection["Neuroprotection"]
style ASM fill:#4fc3f7,stroke:#333,color:#000
style Ceramide fill:#4fc3f7,stroke:#333,color:#000
style SMPD1_mutations fill:#ce93d8,stroke:#333,color:#000
style Niemann_Pick_disease_type fill:#ef5350,stroke:#333,color:#000
style SMPD1_mutations_1 fill:#ce93d8,stroke:#333,color:#000
style Neurodegeneration fill:#4fc3f7,stroke:#333,color:#000
style Ceramide_2 fill:#4fc3f7,stroke:#333,color:#000
style Apoptosis fill:#4fc3f7,stroke:#333,color:#000
style Amitriptyline fill:#4fc3f7,stroke:#333,color:#000
style ASM_3 fill:#4fc3f7,stroke:#333,color:#000
style SREBF2_dysregulation fill:#4fc3f7,stroke:#333,color:#000
style de_novo_cholesterol_synth fill:#4fc3f7,stroke:#333,color:#000
style ABCA1 fill:#4fc3f7,stroke:#333,color:#000
style cholesterol_efflux fill:#4fc3f7,stroke:#333,color:#000
style Ceramide_accumulation fill:#4fc3f7,stroke:#333,color:#000
style Lysosomal_membrane_permea fill:#4fc3f7,stroke:#333,color:#000
style Acid_sphingomyelinase fill:#4fc3f7,stroke:#333,color:#000
style Lysosomal_destabilization fill:#4fc3f7,stroke:#333,color:#000
style UNC1062 fill:#4fc3f7,stroke:#333,color:#000
style ASM_4 fill:#4fc3f7,stroke:#333,color:#000
style Lysosomal_membrane_permea_5 fill:#4fc3f7,stroke:#333,color:#000
style Cathepsin_release fill:#4fc3f7,stroke:#333,color:#000
style Selective_ASM_inhibitors fill:#4fc3f7,stroke:#333,color:#000
style Neuroprotection 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 this gene.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.