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["Neuronal Stress
Protein Aggregates
Damaged Organelles"] -->|"activates"| B["AMPK Kinase
Energy Sensor"]
    A -->|"triggers"| C["mTOR Inhibition
Nutrient Stress Response"]
    
    B -->|"phosphorylates"| D["FOXO1 Transcription Factor
Autophagy Gene Master Regulator"]
    C -->|"releases inhibition"| D
    
    D -->|"translocates to nucleus"| E["FOXO1 Nuclear Translocation
Transcriptional Activation"]
    
    E -->|"transcriptionally upregulates"| F["ATG Gene Expression
LC3, BECN1, ATG7"]
    E -->|"coordinates with"| G["TFEB Transcription Factor
Lysosomal Biogenesis Master Regulator"]
    
    F -->|"increases"| H["Autophagosome Formation
Phagophore Assembly"]
    
    G -->|"translocates to nucleus"| I["TFEB Nuclear Translocation
CLEAR Network Activation"]
    
    I -->|"transcriptionally upregulates"| J["Lysosomal Gene Expression
LAMP1, Cathepsins, V-ATPase"]
    
    J -->|"increases"| K["Lysosomal Biogenesis
Enhanced Degradation Capacity"]
    
    H -->|"forms"| L["Mature Autophagosomes
Cargo-Loaded Vesicles"]
    K -->|"provides"| M["Functional Lysosomes
Acidic Compartments"]
    
    L -->|"fuses with"| N["Autolysosome Formation
Degradative Fusion"]
    M -->|"enables fusion"| N
    
    N -->|"degrades cargo via"| O["Proteolytic Degradation
Cathepsin-Mediated Hydrolysis"]
    
    O -->|"prevents"| P["Autophagosome Accumulation
Traffic Jam Prevention"]
    O -->|"reduces"| Q["Protein Aggregate Burden
Neuronal Protection"]
    
    P -->|"maintains"| R["Cellular Homeostasis
Neuroprotection"]
    Q -->|"prevents"| S["Neurodegeneration
Cell Death"]
    
    R -->|"promotes"| T["Neuronal Survival
Cognitive Preservation"]
    S -->|"preserves"| T

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