Hypothesis Comparison

graph TD
    A["PINK1 accumulation"]
    B["PRKN translocation"]
    C["RAB7A-GTP activation"]
    D["MLCS formation"]
    E["Mitochondrial ubiquitination"]
    F["Lysosomal positioning"]
    G["Autophagosome maturation"]
    H["Mitochondrial fragmentation"]
    I["Defective mitophagy"]
    J["ROS accumulation"]
    K["Neuronal dysfunction"]
    L["Synaptic degeneration"]
    M["RAB7A modulators"]
    N["MLCS stabilizers"]
    O["Neurodegeneration"]

    A -->|"phosphorylates"| B
    B -->|"activates"| C
    C -->|"promotes"| D
    D -->|"facilitates"| E
    C -->|"controls"| F
    D -->|"enables"| G
    E -->|"triggers"| H
    F -->|"impaired when defective"| I
    I -->|"leads to"| J
    J -->|"causes"| K
    K -->|"progresses to"| L
    L -->|"culminates in"| O
    M -->|"therapeutic targeting"| C
    N -->|"stabilizes"| D
    H -->|"contributes to"| I

    classDef mechanism fill:#4fc3f7
    classDef pathology fill:#ef5350
    classDef therapy fill:#81c784
    classDef outcome fill:#ffd54f
    classDef genetics fill:#ce93d8

    class A,B,C,D,E,F,G,H mechanism
    class I,J,K,L pathology
    class M,N therapy
    class O 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