Fig. 5

Lysosomal proteases exhibit distinctive abilities to process α-syn, TDP-43 and tau. a Comparison of the number of cleavage sites within α-syn, TDP-43 and tau for each lysosomal protease relative to total number of cleavage sites. b Hierarchical clustering analysis demonstrating the relative affinity of proteases for α-syn, TDP-43 or tau. Clusters identified are designated to the right. c-e Pairwise correlation analyses with significance values (p-values) of unique versus redundant activity between lysosomal proteases for α-syn (C), TDP-43 (D) and tau (E). A positive score suggests more correlation and a negative score lower correlation between protease cleavage sites. f-q The iceLogo output for each of the serine (F), aspartyl (G-H) and cysteine (I-Q) proteases demonstrating the frequency of particular amino acids at the P4 – P4’ positions of each protease recognition motif within α-syn, TDP-43 and tau. Amino acids that were more frequently seen are above the horizontal axis and those that were less frequently seen are below the horizontal axis. The cleavage site is indicated with a vertical hatched line. *p < 0.05, **p < 0.01, or ***p < 0.001