Fig. 4

Small molecule inhibition of PARP-1/2 reduces the formation of stress-induced TDP-43 foci in mammalian cells. a Veliparib is a small molecule inhibitor of PARP-1/2 activity reported to inhibit the formation of G3BP1-labelled foci in the cytoplasm upon UV treatment [49]. b Exposure to arsenite leads to the formation of TIAR-labelled stress granules in the cytoplasm (arrows). Co-treatment with Veliparib inhibits the formation of TIAR-labelled stress granules. COS-7 cells transfected with TDP-43-YFP were immunostained for TIAR and counterstained with Hoescht. Cells were imaged for TIAR and Hoescht. c Cells were quantified for the presence of cytoplasmic TIAR-labelled stress granules. Mean (± SEM) is presented. One-way ANOVA followed by a Tukey’s test was used for significance. d Under normal conditions (ctrl), TDP-43-YFP diffusely localizes to the nucleus of COS-7 cells. Upon treatment with arsenite, TDP-43-YFP forms foci in the cytoplasm (arrows). The formation of cytoplasmic TDP-43-YFP foci is inhibited by treatment with Veliparib. Cells were counterstained with Hoescht. e Veliparib reduces the accumulation of TDP-43-YFP foci in the cytoplasm. Cells were quantified for the presence of cytoplasmic TDP-43-YFP foci. Mean (± SEM) is presented. One-way ANOVA (p = 0.0002) followed by a Tukey’s test was used for significance. f Hypothetical schematic showing that inhibition of PARP-1/2 activation by Veliparib inhibits the formation of stress-induced TDP-43-YFP foci