Disrupted Ca2+ homeostasis enhances wild-type TDP-43 toxicity.

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Disrupted Ca2+ homeostasis enhances wild-type TDP-43 toxicity. Disrupted Ca2+ homeostasis enhances wild-type TDP-43 toxicity. A, Transgenic worms expressing TDP-43WT treated with either EGTA or dantrolene had increased rates of paralysis compared with untreated controls (p < 0.01 for dantrolene-treated worms versus untreated TDP-43WT controls; p < 0.0001 for EGTA-treated worms versus untreated TDP-43WT controls). TDP-43WT, n = 90; TDP-43WT + dantrolene, n = 90; TDP-43WT + EGTA, n = 90. B, Treatment with dantrolene or EGTA increased neurodegeneration in adults on day 9; TDP-43WT transgenics compared with untreated TDP-43WT transgenics. *p < 0.05 versus TDP-43WT at day 9, ****p < 0.0001 versus TDP-43WT at day 9. C, Similar levels of TDP-43 proteins were detected by Western blotting in untreated TDP-43WT transgenics compared with animals treated with EGTA or dantrolene. Dina Aggad et al. J. Neurosci. 2014;34:12093-12103 ©2014 by Society for Neuroscience