Hypothesis Comparison

graph TD
    A["Nutrient
Starvation"] --> B["ULK1 Complex
Activation"]
    B --> C["PI3K Class III
Complex"]
    C --> D["Autophagosome
Nucleation"]
    D --> E["LC3-I to LC3-II
Conversion"]
    E --> F["Autophagosome
Elongation"]
    F --> G["Mature
Autophagosome"]
    G --> H["STX17
Recruitment"]
    H -->|"LIR motif binding"| I["LC3-II
Recognition"]
    H --> J["SNAP29
Recruitment"]
    H --> K["VAMP8
Recruitment"]
    J --> L["Quaternary SNARE
Complex Formation"]
    K --> L
    I --> L
    L --> M["Autophagosome-Lysosome
Fusion"]
    M --> N["Autolysosome
Formation"]
    N --> O["Cargo Degradation
and Recycling"]
    P["STX17
Dysfunction"] --> Q["Impaired Autophagic
Flux"]
    Q --> R["Protein Aggregate
Accumulation"]
    R --> S["Neurodegeneration"]

    classDef normal fill:#4fc3f7
    classDef pathology fill:#ef5350
    classDef target fill:#ce93d8
    classDef outcome fill:#ffd54f

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

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