Hypothesis Comparison

graph TD
    A["Cellular Aging
Senescence Triggers"]
    B["Mitochondrial Dysfunction
Membrane Permeabilization"]
    C["PINK1/Parkin Pathway
Mitophagy Impairment"]
    D["ATG5/ATG7/LC3B
Autophagy Deficiency"]
    E["Cytoplasmic mtDNA
Accumulation"]
    F["Nuclear Envelope
Breakdown"]
    G["Cytoplasmic dsDNA
Recognition"]
    H["cGAS Activation
Conformational Change"]
    I["ATP and GTP
Substrate Binding"]
    J["cGAMP Synthesis
Second Messenger Production"]
    K["STING Activation
ER Translocation"]
    L["TBK1/IRF3
Phosphorylation Cascade"]
    M["Type I Interferon
Transcriptional Response"]
    N["Pro-inflammatory Cytokines
IL-1beta and TNF-alpha"]
    O["Microglial Activation
M1 Polarization"]
    P["Astrocyte Reactivity
A1 Phenotype"]
    Q["Neuroinflammation
Chronic Activation"]
    R["DNASE2 Deficiency
DNA Clearance Failure"]
    S["Neuronal Death
Synaptic Loss"]
    T["Neurodegeneration
Cognitive Decline"]

    A -->|"triggers"| B
    A -->|"impairs"| C
    A -->|"reduces"| D
    B -->|"releases"| E
    A -->|"causes"| F
    C -->|"fails to clear"| E
    D -->|"accumulates"| E
    F -->|"mixes with"| G
    E -->|"becomes"| G
    G -->|"binds to"| H
    H -->|"utilizes"| I
    I -->|"produces"| J
    J -->|"activates"| K
    K -->|"phosphorylates"| L
    L -->|"induces"| M
    L -->|"promotes"| N
    M -->|"activates"| O
    N -->|"polarizes"| O
    M -->|"induces"| P
    N -->|"activates"| P
    O -->|"drives"| Q
    P -->|"sustains"| Q
    E -->|"overwhelms"| R
    R -->|"perpetuates"| G
    Q -->|"causes"| S
    S -->|"leads to"| 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,F normal
    class C,D,R therapeutic
    class B,E,G,Q,S pathology
    class T outcome
    class H,I,J,K,L,M,N,O,P molecular

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