title: Tetrahydroxystilbene glucoside antagonizes age-related α-synuclein overexpression in the hippocampus of APP transgenic mouse model of Alzheimer's disease.
abstract: OBJECTIVE
  To investigate the mRNA and protein alterations of α-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-β-D-glucoside (TSG) on α-synuclein expression.
  
  
  METHODS
  TSG (120 or 240 μmol 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 α-synuclein increased in hippocampus in 4 month to 16 month old Tg mice compared with age-matched control. α-synuclein protein expression in hippocampus also increased in 4 month to 16 month old Tg mice significantly. Significant down-regulation of α-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 α-synuclein protein in Tg mice was inhibited after treatment with TSG.
  
  
  CONCLUSIONS
  The expression and aggregation of α-synuclein was age-dependently increased in Tg mice. TSG not only prevents over-expression of α-synuclein at an early stage, but also reverses the increased expression of α-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.
authors.affiliation: Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Beijing, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.forename: Shun
authors.initials: S
authors.lastname: Yu
authors.forename: Ruyi
authors.initials: R
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Xing
authors.forename: Yaohua
authors.initials: Y
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Li
mesh_terms: D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D003627:Data Interpretation, Statistical; D005960:Glucosides / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046228:Microarray Analysis; D018697:Nootropic Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D013267:Stilbenes / Q000494:pharmacology*; D051844:alpha-Synuclein / Q000096:biosynthesis*
chemical_list: D016564:Amyloid beta-Protein Precursor; D018076:DNA, Complementary; D005960:Glucosides; D018697:Nootropic Agents; D012333:RNA, Messenger; D013267:Stilbenes; D051844:alpha-Synuclein; C093026:2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside