Hypothesis Comparison

graph TD
    A["Lysosomal Membrane Damage"]
    B["ESCRT-0/I Complex Recruitment"]
    C["Ubiquitinated Protein Recognition"]
    D["CHMP2B Activation"]
    E["ESCRT-III Assembly"]
    F["VPS4 ATPase Recruitment"]
    G["Membrane Scission and Repair"]
    H["CHMP2B Mutations"]
    I["Defective ESCRT-III Function"]
    J["Lysosomal Permeabilization"]
    K["Cathepsin Release"]
    L["Neuronal Cell Death"]
    M["Neurodegeneration"]
    N["ESCRT Enhancement Therapy"]
    O["Lysosome Stabilizers"]
    P["Neuroprotective Outcome"]

    A -->|"damage detection"| B
    B -->|"membrane targeting"| C
    C -->|"protein sorting"| D
    D -->|"complex formation"| E
    E -->|"ATPase activation"| F
    F -->|"membrane dynamics"| G
    G -->|"integrity restoration"| P
    H -->|"genetic mutation"| I
    I -->|"repair failure"| J
    J -->|"enzyme leakage"| K
    K -->|"cellular damage"| L
    L -->|"progressive loss"| M
    D -->|"dysfunction"| I
    N -->|"pathway enhancement"| E
    O -->|"membrane protection"| G

    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 mechanism
    class I,J,K,L,M pathology
    class N,O therapy
    class P outcome
    class H genetics

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