FIGURE 1.

Schematic diagram of major TDP-43 C-terminal fragments (CTFs) and their cleavage sites and functional domains, and the experimental models in which they are most commonly detected. Although CTF-35 is frequently formed in cellular and in vitro assays of TDP-43 proteinopathies, this fragment is rarely observed in ALS or FTLD brain tissue, where CTF-25 predominates. Mouse models of TDP-43 exhibit low levels of both fragments. Thus, cleavage of TDP-43 varies according to model and species.