title: Ginsenoside Rd attenuates beta-amyloid-induced tau phosphorylation by altering the functional balance of glycogen synthase kinase 3beta and protein phosphatase 2A.
abstract: Neurofibrillary tangles are aggregates of hyperphosphorylated tau that are one of the pathological hallmarks of Alzheimer's disease (AD). Tau phosphorylation is regulated by a balance of kinase and phosphatase activities. Our previous study has demonstrated that ginsenoside Rd, one of the principal active ingredients of Pana notoginseng, inhibits okadaic acid-induced tau phosphorylation in vivo and in vitro, but the underlying mechanism(s) is unknown. In this study, we showed that ginsenoside Rd pretreatment inhibited tau phosphorylation at multiple sites in beta-amyloid (Aβ)-treated cultured cortical neurons, and in vivo in both a rat and transgenic mouse model. Ginsenoside Rd not only reduced Aβ-induced increased expression of glycogen synthase kinase 3beta (GSK-3β), the most important kinase involved in tau phosphorylation, but also inhibited its activity by enhancing and attenuating its phosphorylation at Ser9 and Tyr216, respectively. Moreover, ginsenoside Rd enhanced the activity of protein phosphatase 2A (PP-2A), a key phosphatase involved in tau dephosphorylation. Finally, an in vitro biochemical assay revealed that ginsenoside Rd directly affected GSK-3β and PP-2A activities. Thus, our findings provide the first evidence that ginsenoside Rd attenuates Aβ-induced pathological tau phosphorylation by altering the functional balance of GSK-3β and PP-2A.
authors: Department of Neurology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors: Ling
authors: L
authors: Li
authors: Zhirong
authors: Z
authors: Liu
authors: Juanfang
authors: J
authors: Liu
authors: Xuhui
authors: X
authors: Tai
authors: Xinghua
authors: X
authors: Hu
authors: Xuedong
authors: X
authors: Liu
authors: Zhongliang
authors: Z
authors: Wu
authors: Guangyun
authors: G
authors: Zhang
authors: Ming
authors: M
authors: Shi
authors: Gang
authors: G
authors: Zhao
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D036145:Ginsenosides / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D036145:Ginsenosides; D016875:tau Proteins; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D054648:Protein Phosphatase 2; C049863:ginsenoside Rd