Fig. 5: Lipoamide improves nuclear localization of FUS and TDP-43.
From: Small-molecule dissolution of stress granules by redox modulation benefits ALS models
a, Representative images of iPS cell-derived MNs from three independent experiments treated with 0.1% DMSO or 10 µM lipoamide for 1 day, followed by 10 µM arsenite for 5 days in the presence or absence of lipoamide and labeled with TDP-43. The broken lines indicate the outlines of the nuclei. b, Mean ± s.e.m. of nuclear TDP-43 levels normalized to those of unstressed DMSO-treated MNs (control); n = 417–1,741 cells from three independent experiments. P values were determined by a Tukey test. c, Left, images showing recruitment of FUS–GFP to sites of UV laser-induced DNA damage (yellow arrow) in the nuclei (outlined with broken lines) of iPS cells at the indicated times after laser irradiation. Cells were analyzed after 1 h of treatment with lipoamide, followed by 1 h of arsenate stress. Right, mean ± s.d. of relative FUS–GFP signal intensity in response to DNA damage; n = 5 (DMSO) and 7 (lipoamide) cells. d, Left, images of nuclei (outlined with broken lines) of iPS cell-derived MNs expressing FUS-P525L–GFP from three independent experiments cultured for 21 days and then treated with 0.02% DMSO or 20 µM lipoamide for 24 h at the indicated times after laser irradiation. Yellow lines indicate laser-irradiated sites. Right, mean ± s.e.m. of the relative intensity of FUS–GFP at sites of DNA damage after ablation; n = 14 (DMSO) and 18 (lipoamide) cells from three independent experiments. e, Mean ± s.d. of relative full-length STMN2 mRNA levels normalized to those of GAPDH from two independent experiments. In b and e, MNs were treated as in a.
