Transglutaminase-2 Cross-Linking Inhibition Strategy

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

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

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

    G --> K["Neuronal Death
& Cognitive Decline"]
    H --> K
    I --> J
    J --> K

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

    N --> R["Neuroprotection &
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