Hypothesis Comparison

graph TD
    A["MCOLN1 Gene Expression"] --> B["TRPML1 Channel Synthesis"]
    B --> C["Lysosomal Membrane Integration"]
    C --> D["PI(3,5)P2 Binding"]
    C --> E["Low pH Sensing"]
    D --> F["TRPML1 Channel Activation"]
    E --> F
    F --> G["Ca2+ Efflux from Lysosomes"]
    
    subgraph "Calcium Signaling Cascade"
        G --> H["Cytoplasmic Ca2+ Increase"]
        H --> I["Calcineurin Activation"]
        I --> J["TFEB Dephosphorylation"]
    end
    
    subgraph "Lysosomal Function Recovery"
        J --> K["TFEB Nuclear Translocation"]
        K --> L["Lysosomal Gene Transcription"]
        L --> M["Enhanced Autophagy"]
        M --> N["Amyloid Beta Clearance"]
    end
    
    subgraph "Therapeutic Intervention"
        O["TRPML1 Agonist Treatment"] --> F
        P["Calcium Homeostasis Restoration"] --> G
    end
    
    N --> Q["Reduced Neurodegeneration"]
    
    style A fill:#ef5350,stroke:#333,color:#000
    style F fill:#4caf50,stroke:#333,color:#000
    style N fill:#2196f3,stroke:#333,color:#000
    style Q fill:#ff9800,stroke:#333,color:#000

graph TD
    A["CYP46A1 Gene Therapy
Vector Delivery"] -->|"increases"| B["CYP46A1 Enzyme
Expression"]
    B -->|"converts"| C["Cholesterol to
24S-Hydroxycholesterol"]
    C -->|"crosses"| D["Blood-Brain Barrier
Efflux"]
    D -->|"reduces"| E["Brain Cholesterol
Levels"]
    E -->|"disrupts"| F["Lipid Raft
Microdomains"]
    F -->|"decreases"| G["gamma-Secretase
Activity"]
    G -->|"reduces"| H["Amyloid-beta
Production"]
    E -->|"modulates"| I["Cholesterol-dependent
APP Processing"]
    I -->|"shifts to"| J["Alpha-secretase
Pathway"]
    J -->|"increases"| K["sAPP-alpha
Neuroprotective Fragment"]
    H -->|"decreases"| L["Amyloid Plaque
Formation"]
    C -->|"activates"| M["LXR Nuclear
Receptors"]
    M -->|"upregulates"| N["ABCA1 and APOEpsilon
Expression"]
    N -->|"enhances"| O["Cholesterol and
Amyloid Clearance"]
    L -->|"reduces"| P["Neuroinflammation
and Tau Pathology"]
    K -->|"promotes"| Q["Synaptic Plasticity
and Neuronal Health"]
    O -->|"improves"| Q
    P -->|"prevents"| R["Cognitive Decline
and Neurodegeneration"]
    Q -->|"leads to"| R

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