Hypothesis Comparison

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

graph TD
    A["Intestinal Dysbiosis
Pathogenic bacterial
overgrowth"] --> B["Increased Intestinal
Permeability
Leaky gut syndrome"]
    B --> C["LPS Translocation
Bacterial endotoxin
enters circulation"]
    C --> D["TLR4 Activation
Pattern recognition
on immune cells"]
    D --> E["NF-kappaB Signaling
Transcriptional
activation pathway"]
    E --> F["NLRP3 Priming
Upregulation of
inflammasome components"]
    E --> G["Pro-IL1B Expression
Inactive cytokine
precursor synthesis"]
    E --> H["Pro-CASP1 Expression
Inactive caspase-1
precursor synthesis"]
    C --> I["Microglial TLR4
Brain-resident immune
cell activation"]
    I --> J["CNS NLRP3 Priming
Neuroinflammatory
sensitization"]
    K["Neuronal DAMPs
Amyloid-beta aggregates
ATP release"] --> L["NLRP3-PYCARD
Oligomerization
Signal 2 activation"]
    F --> L
    J --> L
    L --> M["Active CASP1
Caspase-1 cleavage
and activation"]
    H --> M
    M --> N["Mature IL1B
Pro-inflammatory
cytokine secretion"]
    G --> N
    N --> O["Sustained Neuroinflammation
Chronic microglial
activation state"]
    O --> P["Blood-Brain Barrier
Dysfunction
Vascular permeability"]
    O --> Q["Oxidative Stress
ROS production
cellular damage"]
    P --> R["Progressive
Neurodegeneration
Cognitive decline"]
    Q --> R
    
    S["Microbiome Remodeling
Therapeutic intervention
probiotic treatment"] --> T["Restored Gut Barrier
Reduced intestinal
permeability"]
    T --> U["Reduced LPS
Translocation
Decreased endotoxemia"]
    U --> V["Prevented NLRP3
Priming
Neuroprotective effect"]
    
    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,B,C pathology
    class D,E,F,G,H,I,J,K,L,M,N molecular
    class O,P,Q normal
    class R outcome
    class S,T,U,V therapeutic