机构：[1]Department of Pharmacy, Xuanwu Hospital of Capital Medical University, 45 Chang?chun Street, Beijing 100053, China首都医科大学宣武医院药物学研究室药学部[2]Beijing Institute for Brain Disorders, Beijing 100053, China[3]Beijing Engineering Research Center for Nerve System Drugs, Beijing 100053, China[4]Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China[5]Key Laboratory for Basic Pharmacology of Ministry of Education, Zunyi Medical College, Zunyi 563000, China
Tau oligomers are the etiologic molecules of Alzheimer's disease, and correlate strongly with neuronal loss and exhibit neurotoxicity. Recent evidence indicates that small tau oligomers are the most relevant toxic aggregate species. The aim of the present study was to investigate the mechanisms of cornel iridoid glycoside (CIG) on tau oligomers and cognitive functions. We injected wortmannin and GF-109203X (WM/GFX, 200?μM each) into the lateral ventricles to induce tau oligomer and memory impairment in rats. When orally administered with CIG at 60 and 120?mg/kg/day for 14?days, CIG decreased the escape latency in the Morris water maze test. We also found that CIG restored the expression of presynaptic p-synapsin, synaptophysin, and postsynaptic density-95 (PSD-95) decreased by WM/GFX in rat cortex. CIG 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 LC3II in vivo and in vitro, suggesting the restoration of autophagy function. These results suggest that CIG could ameliorate memory deficits and regulate memory-associated synaptic proteins through the clearance of tau oligomers accumulation. Moreover, CIG clears tau oligomers by restoring autophagy function.
基金：
This research was supported by the National Natural
Science Foundation of China (Nos. 81703729, 81473373), National
Science and Technology Major Project of China (No. 2015ZX09101-
016), Beijing New Medical Discipline Grant (XK100270569), and Beijing
High-level Health and Technical Personal Plan (Nos. 2011-1-7,
2014-2-014).
第一作者机构：[1]Department of Pharmacy, Xuanwu Hospital of Capital Medical University, 45 Chang?chun Street, Beijing 100053, China[2]Beijing Institute for Brain Disorders, Beijing 100053, China[3]Beijing Engineering Research Center for Nerve System Drugs, Beijing 100053, China[4]Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China
通讯作者：
推荐引用方式(GB/T 7714)：
Yang Cuicui,Li Xuelian,Zhang Li,et al.Cornel iridoid glycoside induces autophagy to protect against tau oligomer neurotoxicity induced by the activation of glycogen synthase kinase-3β.[J].Journal of natural medicines.2019,73(4):717-726.doi:10.1007/s11418-019-01318-3.
APA：
Yang Cuicui,Li Xuelian,Zhang Li,Li Yali,Li Lin&Zhang Lan.(2019).Cornel iridoid glycoside induces autophagy to protect against tau oligomer neurotoxicity induced by the activation of glycogen synthase kinase-3β..Journal of natural medicines,73,(4)
MLA：
Yang Cuicui,et al."Cornel iridoid glycoside induces autophagy to protect against tau oligomer neurotoxicity induced by the activation of glycogen synthase kinase-3β.".Journal of natural medicines 73..4(2019):717-726
