Extended Data Fig. 8: Lipoamide rescues nuclear localization and functioning of ALS-linked proteins.
From: Small-molecule dissolution of stress granules by redox modulation benefits ALS models
a, Left, mean ± s.d. of nuclear-cytoplasmic intensity ratio of FUS and TDP-43 in HeLa cells pre-treated with 10 µM lipoamide (0.1% DMSO as the control) for 1 h followed by 1 mM arsenate for 1 h in the presence of lipoamide. n = 290–603 cells from 3 independent experiments. p values by two-tailed unpaired t-test. Right, representative image of the HeLa cells stained with TDP-43. Arrowheads indicate some of cytoplasmic punctate signals (stress granules). b, Mean ± s.d. of nuclear-cytoplasmic intensity ratio of FUS-GFP in SFPQ-depleted and the control HeLa cells pre-treated with 10 µM lipoamide (0.1% DMSO as the control) for 1 h followed by 1 mM arsenate for 1 h in the presence of lipoamide. n = 450–543 cells from 3 independent experiments. p values by Tukey’s test. c, (Left) time-lapse images of iPSC-derived MNs expressing FUS P525L-GFP cultured for 14 days. Cells were treated with 0.02% DMSO or 20 µM lipoamide for 1 h followed by 20 µM arsenite for indicated minutes in the presence of lipoamide. Broken lines indicate outline of some nuclei. Arrowheads indicate some cytoplasmic FUS P525L foci. (Right) mean ± s.e.m. of number of FUS P525L foci per MN after arsenite treatment. n = 16 (DMSO) and 18 (lipoamide) cells from 3 independent experiments. p value by two-tailed unpaired t-test. d, (Left) representative images of iPSC-derived MNs expressing FUS P525L-GFP cultured for 5 days and then 30 days in the presence of 0.02% DMSO or 20 µM lipoamide. Broken lines indicate outline of some nuclei. (Right) mean ± s.e.m. of nuclear intensity of FUS P525L-GFP, normalized to that in the control (DMSO). n = 64–198 cells from 5 independent experiments. p value by one-sample unpaired t-test.
