Novel Epigenetic Regulation of Alpha-Synuclein Expression in Down Syndrome

Alpha-synuclein ( SNCA ), a presynaptic protein, is significantly reduced in individuals with Down syndrome (DS) and Ts65Dn mice, a mouse model of DS. Methylation analyses of promoter proximal CpG sites indicate similar reduction in Ts65Dn mice compared to control mice. Epigallocatechin-3-gallate (EGCG), a polyphenolic catechin present in green tea extract, increases methylation of SNCA promoter proximal CpG sites and expression in Ts65Dn mice. These results suggest a positive link between CpG methylation and SNCA expression in Down syndrome.