Transglutaminase-2 Cross-Linking Inhibition Strategy

graph TD
    A["""Neuroinflammation<br/>&amp; Calcium Dysregulation"""] -->|"Ca2+ Influx"| B["TG2 Activation<br/>(Transglutaminase-2)"]

    B -->|"Isopeptide Bond<br/>Formation"| C["Tau Cross-Linking<br/>&amp; Aggregation"]
    B -->|"Protein Cross-Linking"| D["Abeta Oligomer<br/>Stabilization"]
    B -->|"ECM Cross-Linking"| E["BBB Disruption<br/>&amp; Matrix Stiffening"]
    B -->|"NF-kappaB Activation"| F["Pro-inflammatory<br/>Cytokine Cascade"]

    C --> G["Neurofibrillary<br/>Tangle Formation"]
    D --> H["Amyloid Plaque<br/>Stabilization"]
    E --> I["Peripheral Immune<br/>Cell Infiltration"]
    F --> J["Chronic<br/>Neuroinflammation"]

    G --> K["Neuronal Death<br/>&amp; Cognitive Decline"]
    H --> K
    I --> J
    J --> K

    L["""TG2 Inhibitor<br/>Therapy"""] -->|"Selective Active-Site<br/>Blockade"| M["TG2 Cross-Linking<br/>Inhibition"]
    M -->|"Reduced Tau<br/>Cross-Linking"| N["Prevented Tangle<br/>Formation"]
    M -->|"Reduced Abeta<br/>Stabilization"| O["Enhanced Abeta<br/>Clearance"]
    M -->|"Preserved BBB<br/>Integrity"| P["Reduced Immune<br/>Infiltration"]
    M -->|"Suppressed NF-kappaB"| Q["Reduced<br/>Neuroinflammation"]

    N --> R["Neuroprotection &amp;<br/>Cognitive Preservation"]
    O --> R
    P --> R
    Q --> R

    style A fill:#ff8a80,stroke:#d32f2f,color:#000
    style L fill:#4fc3f7,stroke:#2196f3,color:#000
    style R fill:#81c784,stroke:#4caf50,color:#000
    style K fill:#ffab91,stroke:#e64a19,color:#000