STAT3 ameliorates cognitive deficits by positively regulatingthe expression of NMDARs in a mouse model of FTDP-17
作者机构：Department of PathophysiologySchool of Basic Medicine and the Collaborative Innovation Center for Brain ScienceKey Laboratory of Ministry of Education of China and Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Clinic Center of Human Gene ResearchUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina State Key Laboratory of OncogenomicsSchool of Chemical Biology and BiotechnologyPeking University Shenzhen Graduate SchoolShenzhenChina Bomedical EngineeringShenzhen PolytechnicShenzhen 518055China Key Laboratory of Modern Toxicology of ShenzhenShenzhen Center for Disease Control and PreventionShenzhen 518055China Co-innovation Center of NeuroregenerationNantong UniversityNantongJiangsu 226001China
出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)
年 卷 期：2021年第6卷第1期
页 面：158-170页
核心收录：
学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学]
基 金：This work was supported in parts by Natural Science Foundation of China(81870846) the Ministry of Science and Technology of China(2016YFC13058001) Sanming Project of Medicine in Shenzhen(SZSM201611090)
主 题：STAT3 inhibited expressing
摘 要：In tauopathies,memory impairment positively strongly correlates with the amount of abnormal tau aggregates;however,how tau accumulation induces synapse impairment is ***,we found that human tau accumulation activated Signal Transduction and Activator of Transcription-1(STAT1)to inhibit the transcription of synaptic N-methyl-D-aspartate receptors(NMDARs).Here,overexpressing human P301L mutant tau(P301L-hTau)increased the phosphorylated level of Signal Transduction and Activator of Transcription-3(STAT3)at Tyr705 by JAK2,which would promote STAT3 translocate into the nucleus and activate ***,STAT3 was found mainly located in the *** study found that P301L-htau acetylated STAT1 to bind with STAT3 in the cytoplasm,and thus inhibited the nuclear translocation and inactivation of *** of STAT3 in STAT3^(flox/flox) mice mimicked P301L-hTau-induced suppression of NMDARs expression,synaptic and memory *** STAT3 rescued P301L-hTau-induced synaptic and cognitive deficits by increasing NMDARs *** study proved that STAT3 positively regulated NMDARs transcription through direct binding to the specific GAS element of NMDARs *** findings indicate that accumulated P301L-hTau inactivating STAT3 to suppress NMDARs expression,revealed a novel mechanism for tau-associated synapse and cognition deficits,and STAT3 will hopefully serve as a potential pharmacological target for tauopathies treatment.
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