Fig. 5: NAM supplementation reverses mitochondrial respiration defect and improves neuronal morphology in ALS MNs.
From: ALS motor neurons exhibit hallmark metabolic defects that are rescued by SIRT3 activation
a Measurements of mitochondrial NAD+ levels in healthy and ALS MNs after NAM supplementation revealed increased mitochondrial NAD+ availability in ALS MNs. b WT and ALS iPSC-derived MNs were treated with either H2O or NAM 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. NAM supplementation 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. c–e Measurements of basal respiration, ATP production, and spare respiration, respectively, in healthy and ALS MNs treated with water as a control (purple) or 0.5 mM NAM (orange). f Representative images of ISL1+SMI32+ MNs of BJ-SOD1L144F and BJ-TDP43G298S illustrating NAM supplementation promotes healthier neuronal morphologies. MN cell body sizes are outlined by white dotted lines. Scale bars, 50 μm. g Measurement of soma size and primary neurites shows overall improvement in neuronal morphology in NAM supplemented ALS MNs. ***p < 0.001, ns non-significant; two-tailed t-test.
