Figure 4.

Seed-dependent and self-templating intracellular TDP-43 aggregation. The mechanisms by which intracellular aggregates cause cell death are proposed to be as follows: Insoluble TDP-43 deposited as amyloid-like fibrils is produced or taken up in the first cell and released into the extracellular space via membrane leakage or exosome. Introduced aggregates nucleate additional intracellular aggregation in adjacent cells. Increased levels of aggregates cause cellular dysfunction and, finally, cell death.