Fig. 5: Schematic model of FZD1 and FZD7 regulation by SIRT2 in AD. | Molecular Psychiatry

Fig. 5: Schematic model of FZD1 and FZD7 regulation by SIRT2 in AD.

From: Epigenetic repression of Wnt receptors in AD: a role for Sirtuin2-induced H4K16ac deacetylation of Frizzled1 and Frizzled7 promoters

Fig. 5

Scheme representing the nuclear localisation of the histone deacetylase SIRT2, its phosphatase PP2C and the epigenetic regulation of FZD1 and FZD7 in the healthy brain and in AD. In the healthy brain, high levels of H4K16ac and low levels of SIRT2 coexist at FZD1 and FZD7 prompters. In addition, high levels of FoxO1 are present at FZD7 promoter, altogether leading to FZD1 and FZD7 transcription. In AD, increased nuclear levels of the phosphatase PP2C activates SIRT2 by removing its inhibitory phosphorylation. In turn, FoxO1 recruits SIRT2 to FZD1 and FZD7 promoters leading to reduced levels of H4K16ac and impairing FZD1 and FZD7 transcription.

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