FIGURE 9.

Seeding ability of peptide fibrils for TDP-43 deletion mutants. A, series of deletion mutants of WT-TDP-43 lacking a 40-amino acid sequence of the C-terminal region were constructed and expressed in SH-SY5Y cells. After 48 h of incubation, cells were fractionated into Sar-soluble (sup) and Sar-insoluble (ppt). Immunoblotting of sup was conducted using anti-TDP-43 and immunoblotting of ppt was conducted using anti-pS409/410 antibodies. B, TDP-43 peptide fibrils of 274–313 (B) and 314–353 (C) were introduced into cells expressing these WT-TDP-43 deletion mutants. The sup and ppt fractions were prepared and immunoblotted. Black arrowhead indicates endogenous full-length TDP-43, and white arrowhead indicates deletion mutant of TDP-43. D, based on a report of moderate similarity between C-terminal regions of TDP-43 and PrP (23), regions corresponding to TDP-43 (234–273, 274–313 and 314–353) are indicated on the alignment of human TDP-43 C-terminal region and human prion protein (PrP). *, identical amino acid residues.