Hypothesis Comparison

graph TD
    subgraph "Tau Pathology"
        A["Tau Aggregates"]
        B["Misfolded Tau"]
    end
    
    subgraph "HSP90 System"
        C["HSP90AA1"]
        D["ATP Binding Domain"]
        E["Allosteric Binding Pocket"]
        F["Co-chaperones"]
    end
    
    subgraph "Therapeutic Intervention"
        G["Allosteric Modulators"]
        H["Enhanced Conformation"]
        I["ATP-dependent Cycling"]
    end
    
    subgraph "Cellular Outcomes"
        J["Disaggregation Complex"]
        K["Tau Clearance"]
        L["Protein Quality Control"]
        M["Neuronal Protection"]
    end
    
    N["Conformational States"]
    O["Client Protein Interaction"]
    
    A -->|"accumulation"| B
    B -->|"targets"| C
    G -->|"binds to"| E
    E -->|"modulates"| C
    C -->|"contains"| D
    C -->|"recruits"| F
    G -->|"induces"| H
    H -->|"enables"| I
    C -->|"adopts"| N
    N -->|"enhances"| O
    F -->|"forms"| J
    I -->|"drives"| J
    J -->|"promotes"| K
    K -->|"improves"| L
    L -->|"leads to"| M
    
    style A fill:#ff9999
    style M fill:#99ff99
    style G fill:#9999ff

graph TD
    A["Amyloid-beta plaques<br/>and inflammatory signals"] --> B["Microglial activation<br/>to DAM phenotype"]
    B --> C["ACSL4 gene<br/>transcriptional upregulation"]
    C --> D["ACSL4 protein<br/>enzymatic activity increase"]
    D --> E["Arachidonic acid esterification<br/>to arachidonyl-CoA"]
    D --> F["Adrenic acid esterification<br/>to adrenoyl-CoA"]
    E --> G["PE-AA synthesis<br/>in membrane phospholipids"]
    F --> H["PE-AdA synthesis<br/>in membrane phospholipids"]
    G --> I["PUFA-PE membrane<br/>substrate accumulation"]
    H --> I
    B --> J["GPX4 downregulation<br/>and GSH depletion"]
    I --> K["Ferroptotic priming<br/>state establishment"]
    J --> K
    L["Iron accumulation<br/>in brain tissue"] --> M["Fenton reaction<br/>hydroxyl radical generation"]
    M --> N["Lipid peroxidation<br/>of PUFA-PE substrates"]
    K --> N
    N --> O["Membrane integrity<br/>disruption and damage"]
    O --> P["Microglial ferroptotic<br/>cell death execution"]
    P --> Q["Pro-inflammatory<br/>mediator release"]
    P --> R["Reduced phagocytic<br/>clearance capacity"]
    Q --> S["Neuroinflammation<br/>amplification"]
    R --> T["Amyloid plaque<br/>accumulation"]
    S --> U["Neuronal dysfunction<br/>and cognitive decline"]
    T --> U

    classDef normal fill:#4fc3f7,stroke:#2196f3
    classDef therapeutic fill:#81c784,stroke:#4caf50
    classDef pathology fill:#ef5350,stroke:#f44336
    classDef outcome fill:#ffd54f,stroke:#ff9800
    classDef molecular fill:#ce93d8,stroke:#9c27b0

    class A,L pathology
    class B,C,D,E,F,G,H,I,J,M,N normal
    class K,O,P molecular
    class Q,R,S,T outcome
    class U pathology