Figure 4. NAD⁺ boosters reduce Aβ proteotoxicity and aggregation in GMC101 worms and cells.

a–b, MSR transcripts in GMC101 worms treated with nicotinamide riboside (a, NR) or Olaparib (b, AZD). a–b, n=3 biologically independent samples. c, Mobility of GMC101 treated with NR (n=50 worms) or AZD (n=39 worms). **P≤0.001 (AZD,0.006); ****P≤0.0001 (NR). d, Percentage of dead D8 adult GMC101 after NR or AZD (n=3 independent experiments). e, Western-blot of amyloid aggregation in GMC101 after NR or AZD (n=3 biologically independent samples for all groups). f, Mobility of GMC101 treated with NR upon atfs-1 RNAi feeding (ev, n=52; atfs-1, n=38; NR, n=40; NR, atfs-1, n=41 worms). ***P≤0.001 (atfs-1,0.0006). g, Percentage of dead D8 adult GMC101 treated with NR upon atfs-1 RNAi (n=5 biologically independent samples). h, Amyloid aggregation in NR-treated GMC101 upon atfs-1 RNAi feeding (WB representative of 2 biological replicates). i, Mobility of NR-treated GMC101 upon dct-1 RNAi (ev, n=41; dct-1, n=40; NR, n=39; NR, dct-1, n=50 worms). j, Percentage of dead D8 adult GMC101 treated with NR upon dct-1 RNAi (n=5 biologically independent samples). k, Amyloid aggregation immunoblot in NR-treated GMC101 upon dct-1 RNAi (n=3 biologically independent samples). l, Confocal images of APP_Swe SH-SY5Y cells stained with anti-β-Amyloid 1-42, after 24 h NR treatment. Scale bar, 10μm. Values in the figure are mean ± s.e.m. *P<0.05; **P≤0.01; ***P ≤ 0.001; ****P≤0.0001; n.s., non-significant. Throughout the figure, overall differences between conditions were assessed by two-way ANOVA. Differences for individual genes or two groups were assessed using two-tailed t tests (95% confidence interval). All experiments were performed independently at least twice. ev, scrambled RNAi; A.U., arbitrary units. See also Extended Data Fig. 6. For uncropped gel source data, see Supplementary Fig. 1. For all the individual p values, see the Fig. 4 Spreadsheet file.