Hypothesis Comparison

graph TD
    A["Pathological Tau<br/>Oligomers"]
    B["SNAP25<br/>Linker Domain"]
    C["SNARE Complex<br/>Formation"]
    D["Syntaxin-1A"]
    E["VAMP2"]
    F["Synaptic Vesicle<br/>Endocytosis"]
    G["Tau-SNAP25<br/>Binding"]
    H["SNARE Complex<br/>Disruption"]
    I["Vesicle Recycling<br/>Impairment"]
    J["Neurotransmitter<br/>Release Defects"]
    K["Synaptic<br/>Dysfunction"]
    L["Cognitive<br/>Decline"]
    M["SNAP25<br/>Inhibitors"]
    N["Tau Aggregation<br/>Prevention"]

    A -->|"pathological binding"| B
    B --> C
    C --> D
    C --> E
    D --> F
    E --> F
    A --> G
    B --> G
    G -->|"complex destabilization"| H
    H -->|"impaired recycling"| I
    F -->|"normal process"| I
    I -->|"reduced release"| J
    J -->|"synaptic failure"| K
    K -->|"neurodegeneration"| L
    M -->|"therapeutic intervention"| G
    N -->|"prevention strategy"| A

    classDef normal fill:#4fc3f7
    classDef therapeutic fill:#81c784
    classDef pathology fill:#ef5350
    classDef outcomes fill:#ffd54f
    classDef molecular fill:#ce93d8

    class D,E,F,C normal
    class M,N therapeutic
    class A,G,H,I,J,K pathology
    class L outcomes
    class B molecular

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