Fig. 6: A small molecule activator of SIRT3, but not riluzole or edaravone, improves neuronal morphologies in ALS MNs.
From: ALS motor neurons exhibit hallmark metabolic defects that are rescued by SIRT3 activation
a Representative western blot and CESTA melt curves in intact cell for SIRT3 target with C12 (at 20 μM). b Western blot analyses at day 31 revealed reduction in mitochondria Ac-K signals in ALS MNs upon C12 treatment. c WT and ALS iPSC-derived MNs were treated with either DMSO/H2O or C12/riluzole/edaravone from days 28 to 35. Number of ISL1+ MNs were quantified and normalized to number of ISL1+ MNs in respective cell lines at day 28. C12, riluzole, and edaravone treatment prevents MN death in ALS MNs. One-way ANOVA with Tukey’s multiple comparisons post hoc test has been performed to analyze survival of wild-type and ALS MNs on day 35. d–f qPCR quantification of ER stress transcripts CHOP and spliced XBP1 (sXBP1) in MN cultures at day 31 treated with controls or C12/riluzole/edaravone. Fold changes are normalized to expression levels of respective mRNA in BJ-iPS MNs treated with DMSO or water. Gene expression was normalized to ACTINB and HPRT. ***p < 0.001, ns non-significant; two-tailed t-test.
