Cornel iridoid glycoside induces autophagy to protect against tau oligomer neurotoxicity induced by activation of glycogen synthase kinase-3β
作者单位：Department of PharmacyXuanwu Hospital of Capital Medical UniversityBeijing Institute for Brain DisordersBeijing Engineering Research Center for Nerve System DrugsKey Laboratory for Neurodegenerative Diseases of Ministry of Education Key Laboratory for Basic Pharmacology of Ministry of EducationZunyi Medical College
会议名称：《2019全国老年痴呆与认知障碍相关疾病学术大会》
会议日期：2019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：cornel iridoid glycoside autophagy tau oligomer glycogen synthase kinase-3β
摘 要：Tau oligomers are the etiologic molecules of Alzheimer disease(AD),and correlate strongly with neuronal loss and exhibit *** evidence indicates that small tau oligomers are the most relevant toxic aggregate *** aim of the present study was to investigate the mechanisms of cornel iridoid glycoside(CIG) on tau oligomers and cognitive *** injected wortmannin and GF-109203 X(WM/GFX,200 μmol·L each) into the lateral ventricles to induce tau oligomer and memory impairment in *** orally administered with CIG at 60 and 120 mg·kg-1 per day for 14 d,CIG decreased the escape latency in Morris water maze *** also found that CIG restored the expression of presynaptic p-synapsin,synaptophysin,and postsynaptic density-95(PSD-95) decreased by WM/GFX in rat *** reduced the accumulation of tau oligomers in the brain of WM/GFX rats and in cells transfected with wild type glycogen synthase kinase-3β(wtGSK-3β).In addition,CIG up-regulated the levels of ATG7,ATG12,Beclin-1,and LC3 II in vivo and in vitro,suggesting the restoration of autophagy *** results suggest that CIG could ameliorate memory deficits and regulate memory-associated synaptic proteins through the clearance of tau oligomers ***,CIG clears tau oligomers by restoring autophagy function.