Figure 1.

FK866 acts within axons to delay degeneration after injury. (a) The salvage pathway of NAD biosynthesis from nicotinamide (Nam) and nicotinic acid (Na). Only NAD biosynthesis from Nam is sensitive to FK866, which potently inhibits NAMPT while having no effect on nicotinic acid phosphoribosyltransferase (NaPRT).²⁹ The reaction catalysed by bacterial NMN deamidase is also shown. (b) SCG explants were treated with 100 nM FK866 for the indicated times, and then the whole explants (top panel) or the cell bodies (bottom left panel) and neurite fractions (bottom right panel) were separately collected. NAD was determined with an HPLC-based method (see Materials and Methods; n=3, mean and S.D. shown). (c) SCG neurites untreated (top panels) or treated with 100 nM FK866 the day before transection (bottom panels) and imaged after transection at the indicated time points. (d) SCG explants were treated with 100 nM FK866 1 day before or at the indicated times after cutting their neurites. Degeneration index was calculated from three fields in 2–4 independent experiments. The effect of treatment is highly significant when the drug is preincubated or added at 0–4 h after cut (mean ±S.E.M., n=6–12, one-way ANOVA followed by Bonferroni's post-hoc test, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, compared with untreated)