Hypothesis Comparison

graph TD
    A["Expanded trinucleotide
repeat transcripts
(HTT, DMPK, C9orf72)"] --> B["Formation of toxic
RNA secondary
structures"]
    B --> C["RNA gain-of-function
toxicity mechanisms"]
    C --> D["Sequestration of
RNA-binding proteins"]
    C --> E["Formation of nuclear
RNA foci/inclusions"]
    D --> F["Disrupted RNA
splicing and
processing"]
    E --> F
    F --> G["Cellular dysfunction
and neurodegeneration"]
    
    H["CRISPR-Cas13d/CasRx
RNA-targeting system"] --> I["Guide RNA design
targeting repeat
sequences"]
    I --> J["Specific binding to
expanded repeat
transcripts"]
    J --> K["RNA sequestration
without degradation"]
    K --> L["Prevention of toxic
secondary structure
formation"]
    L --> M["Reduced RNA-binding
protein sequestration"]
    L --> N["Dissolution of
pathological RNA foci"]
    M --> O["Restored cellular
RNA homeostasis"]
    N --> O
    O --> P["Preserved residual
protein production
and neuroprotection"]

    classDef pathology fill:#ef5350
    classDef therapeutic fill:#81c784
    classDef normal fill:#4fc3f7
    classDef outcome fill:#ffd54f
    classDef molecular fill:#ce93d8
    
    class A,B,C,D,E,F,G pathology
    class H,I,J,K,L,M,N therapeutic
    class O normal
    class P 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