Ribosylation-Derived Advanced Glycation End Products Induce Tau Hyperphosphorylation Through Brain-Derived Neurotrophic Factor Reduction | |
Wu, Beibei1; Wang, Yujing1; Shi, Chenggang1; Chen, Yao2; Yu, Lexiang1; Li, Juan3; Li, Weiwei5; Wei, Yan1; He, Rongqiao1,4 | |
刊名 | JOURNAL OF ALZHEIMERS DISEASE |
2019 | |
卷号 | 71期号:1页码:291-305 |
关键词 | Advanced glycation end products brain-derived neurotrophic factor GSK-3 beta oxidative stress ribosylation tau hyperphosphorylation |
ISSN号 | 1387-2877 |
DOI | 10.3233/JAD-190158 |
通讯作者 | Wei, Yan(yanwei@ibp.ac.cn) ; He, Rongqiao(herq@ibp.ac.cn) |
英文摘要 | Advanced glycation end products (AGEs) have been implicated in the disease process of diabetes mellitus. They have also been found in senile plaques and neurofibrillary tangles in the brains of Alzheimer's disease patients. Furthermore, abnormally high levels of D-ribose and D-glucose were found in the urine of patients with type 2 diabetes mellitus, suggesting that diabetic patients suffer from dysmetabolism of not only D-glucose but also D-ribose. In the present study, intravenous tail injections of ribosylated rat serum albumin (RRSA) were found to impair memory in rats, but they did not markedly impair learning, as measured by the Morris water maze test. Injections of RRSA were found to trigger tau hyperphosphorylation in the rat hippocampus via GSK-3 beta activation. Tau hyperphosphorylation and GSK-3 beta activation were also observed in N2a cells in the presence of ribosylation-derived AGEs. Furthermore, the administration of ribosylation-derived AGEs induced the suppression of brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB). Both GSK-3 beta inhibition and BDNF treatment decreased the levels of phosphorylated tau in N2a cells. In particular, the administration of BDNF could rescue memory failure in ribosylated AGE-injected rats. Ribosylation-derived AGEs downregulated the BDNF-TrkB pathway in rat brains and N2a cells, leading to GSK-3 beta activation-mediated tau hyperphosphorylation, which was involved in the observed rat memory loss. Targeting ribosylation may be a promising therapeutic strategy to prevent Alzheimer's disease and diabetic encephalopathies. |
资助项目 | National Key Research and Development Program of China[2016YFC1305900] ; National Key Research and Development Program of China[2016YFC1306300] ; Beijing Municipal Science and Technology Project[Z161100000217141] ; Beijing Municipal Science and Technology Project[Z161100000216137] ; Natural Scientific Foundation of China NSFC[31670805] ; Natural Scientific Foundation of China NSFC[81573763] ; Youth Innovation Promotion Association CAS[2017132] ; 973 Project[2012CB911004] ; External Cooperation Program of BIC, Chinese Academy of Sciences[GJHZ201302] |
WOS关键词 | GROWTH-FACTOR EXPRESSION ; D-RIBOSE ; ALZHEIMERS-DISEASE ; PROTEIN ; MEMORY ; BDNF ; TERM ; HIPPOCAMPUS ; MECHANISM ; STRESS |
WOS研究方向 | Neurosciences & Neurology |
语种 | 英语 |
出版者 | IOS PRESS |
WOS记录号 | WOS:000484216500023 |
资助机构 | National Key Research and Development Program of China ; Beijing Municipal Science and Technology Project ; Natural Scientific Foundation of China NSFC ; Youth Innovation Promotion Association CAS ; 973 Project ; External Cooperation Program of BIC, Chinese Academy of Sciences |
内容类型 | 期刊论文 |
源URL | [http://ir.psych.ac.cn/handle/311026/29836] |
专题 | 心理研究所_脑与认知科学国家重点实验室 |
通讯作者 | Wei, Yan; He, Rongqiao |
作者单位 | 1.Univ Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, Beijing, Peoples R China 2.Southwest Med Univ, Luzhou, Sichuan, Peoples R China 3.Chinese Acad Sci, Inst Psychol, Key Laboratoty Mental Hlth, Beijing, Peoples R China 4.Capital Med Univ, Alzheimers Dis Ctr, Beijing Inst Brain Disorders, Beijing, Peoples R China 5.Peking Univ Hosp, Beijing, Peoples R China |
推荐引用方式 GB/T 7714 | Wu, Beibei,Wang, Yujing,Shi, Chenggang,et al. Ribosylation-Derived Advanced Glycation End Products Induce Tau Hyperphosphorylation Through Brain-Derived Neurotrophic Factor Reduction[J]. JOURNAL OF ALZHEIMERS DISEASE,2019,71(1):291-305. |
APA | Wu, Beibei.,Wang, Yujing.,Shi, Chenggang.,Chen, Yao.,Yu, Lexiang.,...&He, Rongqiao.(2019).Ribosylation-Derived Advanced Glycation End Products Induce Tau Hyperphosphorylation Through Brain-Derived Neurotrophic Factor Reduction.JOURNAL OF ALZHEIMERS DISEASE,71(1),291-305. |
MLA | Wu, Beibei,et al."Ribosylation-Derived Advanced Glycation End Products Induce Tau Hyperphosphorylation Through Brain-Derived Neurotrophic Factor Reduction".JOURNAL OF ALZHEIMERS DISEASE 71.1(2019):291-305. |
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