Ginsenoside Rd attenuates Aβ-induced tau phosphorylation via altering the functional balance of glycogen synthase kinase-3β and protein phosphatase-2A
作者单位：Xijing HospitalThe Fourth Military Medical University
会议名称：《中国神经科学学会第十届全国学术会议》
会议日期：2013年
学科分类：1008[医学-中药学(可授医学、理学学位)] 1006[医学-中西医结合] 100602[医学-中西医结合临床] 10[医学]
关 键 词：Ginsenoside Rd tau phosphorylation glycogen synthase kinase-3beta protein phosphatase-2A Alzheimer’s disease
摘 要：Objectives Neurofibrillary tangles are aggregates of hyperphosphorylated tau protein that are one of pathological hallmarks of Alzheimer’s disease（AD）.The phosphorylation level of tau protein is regulated by a balance of kinase and phosphatase *** previous study has demonstrated that ginsenoside Rd,one of the principal active ingredients of Pana notoginseng,inhibits okadaic acid-induced phosphorylation of tau protein in vivo and in vitro,but the underlying mechanism（s） is *** In this study,using multiple AD models,including Ap-treated cultured cortical neurons,an AD rat model with Ap injection into hippocampus CA1 and APP transgenic mice,we explored possible mechanisms of inhibitory effects of ginsenoside-Rd on tau protein phosphorylation by Western blotting analysis and an in vitro biochemical *** Ginsenoside Rd pretreatment inhibited tau protein phosphorylation at multiple sites（Serl99/202,Ser396 and Ser404）.Ginsenoside Rd not only reduced Ap-induced increased expression of glycogen synthase kinase 3β（GSK-3β）,the most important kinase involving tau phosphorylation,but also inhibited its activity by enhancing and attenuating its phosphorylation at Ser9 and Tyr216,***,ginsenoside Rd enhanced the activity of protein phosphatase 2A（PP-2A）,a key phosphatase involving tau protein ***,an in vitro biochemical assay revealed that ginsenoside Rd could affect GSK-3β and PP-2A activities in a direct *** Thus,our findings provide the first evidence that ginsenoside Rd attenuates Ap-induced tau protein phosphorylation