Tetrahydroxystilbene glucoside antagonizes age-related α-synuclein overexpression in the hippocampus of APP transgenic mouse model of Alzheimer's disease

Purpose: To investigate the mRNA and protein alterations of -synuclein in the brain of Alzheimer's disease-like mouse model at the different ages, and to evaluate the effects of 2,3,5,4 � -tetrahydroxy stilbene-2-O--D-glucoside (TSG) on -synuclein expression. Methods: TSG (120 or 240mol kg −1 d −1 ) was intragastrically administered to APPV717I transgenic (Tg) mice at 4- or 10-month-old for 6 months. Results: mRNA expression of -synuclein increased in hippocampus in 4 month to 16 month old Tg mice compared with age- matched control.-synuclein protein expression in hippocampus also increased in 4 month to 16 month old Tg mice significantly. Significant down-regulation of -synuclein mRNA and protein expression in hippocampus was found after treatment of TSG for 6 months in both 10- and 16-month-old Tg mice. Production of dimer and tetramer of -synuclein protein in Tg mice was inhibited after treatment with TSG. Conclusions: The expression and aggregation of -synuclein was age-dependently increased in Tg mice. TSG not only prevents over-expression of -synuclein at an early stage, but also reverses the increased expression of -synuclein and inhibits the aggregation at the late stage of Tg mice. TSG may have potential to the prevention and treatment of Alzheimer's diseases.