Transglutaminase-2 Cross-Linking Inhibition Strategy

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Protein aggregation cross-seeding across neurodegenerative diseases

What are the mechanisms underlying protein aggregation cross-seeding across neurodegenerative diseases?

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graph TD
    tau["tau"] -->|cross-seeds| alpha_synuclein["alpha-synuclein"]
    alpha_synuclein_1["alpha-synuclein"] -->|cross-seeds| tau_2["tau"]
    TDP_43["TDP-43"] -->|cross-seeds| tau_3["tau"]
    TDP_43_4["TDP-43"] -->|cross-seeds| alpha_synuclein_5["alpha-synuclein"]
    tau_6["tau"] -->|cross-seeds| TDP_43_7["TDP-43"]
    tau_8["tau"] -->|associated with| alzheimers_disease["alzheimers_disease"]
    alpha_synuclein_9["alpha-synuclein"] -->|associated with| parkinsons_disease["parkinsons_disease"]
    TDP_43_10["TDP-43"] -->|associated with| frontotemporal_dementia["frontotemporal_dementia"]
    tau_11["tau"] -->|associated with| frontotemporal_dementia_12["frontotemporal_dementia"]
    alpha_synuclein_13["alpha-synuclein"] -->|associated with| lewy_body_dementia["lewy_body_dementia"]
    cross_seeding["cross_seeding"] -->|associated with| multiple_system_atrophy["multiple_system_atrophy"]
    TGM2["TGM2"] -->|encodes| transglutaminase_2["transglutaminase-2"]
    style tau fill:#4fc3f7,stroke:#333,color:#000
    style alpha_synuclein fill:#4fc3f7,stroke:#333,color:#000
    style alpha_synuclein_1 fill:#4fc3f7,stroke:#333,color:#000
    style tau_2 fill:#4fc3f7,stroke:#333,color:#000
    style TDP_43 fill:#4fc3f7,stroke:#333,color:#000
    style tau_3 fill:#4fc3f7,stroke:#333,color:#000
    style TDP_43_4 fill:#4fc3f7,stroke:#333,color:#000
    style alpha_synuclein_5 fill:#4fc3f7,stroke:#333,color:#000
    style tau_6 fill:#4fc3f7,stroke:#333,color:#000
    style TDP_43_7 fill:#4fc3f7,stroke:#333,color:#000
    style tau_8 fill:#4fc3f7,stroke:#333,color:#000
    style alzheimers_disease fill:#ef5350,stroke:#333,color:#000
    style alpha_synuclein_9 fill:#4fc3f7,stroke:#333,color:#000
    style parkinsons_disease fill:#ef5350,stroke:#333,color:#000
    style TDP_43_10 fill:#4fc3f7,stroke:#333,color:#000
    style frontotemporal_dementia fill:#ef5350,stroke:#333,color:#000
    style tau_11 fill:#4fc3f7,stroke:#333,color:#000
    style frontotemporal_dementia_12 fill:#ef5350,stroke:#333,color:#000
    style alpha_synuclein_13 fill:#4fc3f7,stroke:#333,color:#000
    style lewy_body_dementia fill:#ef5350,stroke:#333,color:#000
    style cross_seeding fill:#ffd54f,stroke:#333,color:#000
    style multiple_system_atrophy fill:#ef5350,stroke:#333,color:#000
    style TGM2 fill:#ce93d8,stroke:#333,color:#000
    style transglutaminase_2 fill:#4fc3f7,stroke:#333,color:#000

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