Hypothesis Comparison

graph TD
    A["APOE4 Risk Variant<br/>Cys112->Arg112"] --> B["Aberrant Domain Interaction<br/>N-terminal and C-terminal"]
    B --> C["Misfolded APOE4 Protein<br/>Compact Dysfunctional State"]
    
    subgraph "Chaperone Enhancement Strategy"
        D["HSPA1A Upregulation<br/>HSP70 Expression"]
        E["HSP90AA1 Activation<br/>ATP-dependent Folding"]
        F["DNAJB1 Co-chaperone<br/>J-domain Protein"]
        G["FKBP5 Modulation<br/>Immunophilin Activity"]
    end
    
    C --> H["Cellular Stress Response<br/>Protein Quality Control"]
    H --> D
    H --> E
    D --> I["HSP70-APOE4 Complex<br/>Substrate Binding"]
    E --> J["HSP90-Mediated Refolding<br/>Conformational Maturation"]
    F -->|"Co-chaperone Function"| I
    G -->|"Regulatory Interaction"| J
    
    I --> K["Chaperone-Assisted<br/>Protein Refolding"]
    J --> K
    K --> L["Restored APOE4<br/>Functional Conformation"]
    L --> M["Enhanced Lipid Transport<br/>Amyloid-beta Clearance"]
    
    subgraph "Therapeutic Outcomes"
        N["Reduced Neurodegeneration"]
        O["Improved Cognitive Function"]
        P["Neuroprotective Effects"]
    end
    
    M --> N
    M --> O
    M --> P

    style A fill:#ef5350,stroke:#333,color:#000
    style C fill:#ef5350,stroke:#333,color:#000
    style L fill:#4caf50,stroke:#333,color:#000
    style M fill:#4caf50,stroke:#333,color:#000