TREM2-Mediated Selective Aggregate Clearance Pathway

graph TD
    A["Pathological Protein Aggregates"] --> B["Cross-Seeded Heterocomplexes"]
    A --> C["Homologous Aggregates"]

    B --> D["Uniquely Toxic Conformations"]
    D --> E["Enhanced Neuronal Damage"]

    F["TREM2 on Microglia"] --> G["Lipid Ligand Recognition"]
    G --> H["TREM2-DAP12 Signaling"]
    H --> I["SYK Kinase Activation"]

    I --> J["PI3K/AKT Pathway"]
    I --> K["PLCgamma Calcium Flux"]

    J --> L["Phagocytic Cup Formation"]
    K --> L

    L --> M["Selective Aggregate Recognition"]
    M --> N["Cross-Seeded Aggregate Uptake"]
    M --> O["Homologous Aggregate Sparing"]

    N --> P["Lysosomal Degradation"]
    P --> Q["Clearance of Toxic Species"]

    R["TREM2 Agonist Therapy"] --> S["Enhanced TREM2 Surface Expression"]
    S --> T["Boosted Phagocytic Capacity"]
    T --> M

    Q --> U["Reduced Cross-Seeding Cascade"]
    U --> V["Slowed Neurodegeneration"]

    style A fill:#4a1942,stroke:#ce93d8,color:#e0e0e0
    style F fill:#1a3a4a,stroke:#4fc3f7,color:#e0e0e0
    style N fill:#1a3a2a,stroke:#81c784,color:#e0e0e0
    style V fill:#2a3a1a,stroke:#c5e1a5,color:#e0e0e0