Fig. 6.

Cask promoter activity is regulated in an NAD⁺/SIRT1-dependent manner. a The ~2 kb upstream region of the Cask gene is schematically shown. There are two potential Oct-1 binding sites. b, c Relative luciferase activities driven by an ~2 kb Cask promoter fragment were measured in HEK293 cells cotransfected with the reporter construct and a Sirt1 minigene (b) or its promoter-only control vector (c) with treatment of FK866 (100 nM), FK866 (100 nM) plus NMN (100 μM), NMN (100 μM), or EX527 (10 μM). Luciferase activities were normalized to those of DMSO-treated control cells (n = 9; *p < 0.05, one-way ANOVA with LSD post hoc test). Data are presented as mean ± SE. d A proposed model for the relationship between age-associated, NAD⁺/SIRT1-mediated reduction in Cask expression and cognitive hypersensitivity in old mice