Ribosylation-Derived Advanced Glycation End Products Induce Tau Hyperphosphorylation Through Brain-Derived Neurotrophic Factor Reduction

doi:10.3233/JAD-190158

	Ribosylation-Derived Advanced Glycation End Products Induce Tau Hyperphosphorylation Through Brain-Derived Neurotrophic Factor Reduction
	Wu, Beibei 1; Wang, Yujing 1; Shi, Chenggang 1; Chen, Yao 2; Yu, Lexiang 1; Li, Juan3 ; Li, Weiwei 5; Wei, Yan 1; He, Rongqiao 1,4
通讯作者	Wei, Yan(yanwei@ibp.ac.cn) ; He, Rongqiao(herq@ibp.ac.cn)
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.
关键词	Advanced glycation end products brain-derived neurotrophic factor GSK-3 beta oxidative stress ribosylation tau hyperphosphorylation
	2019
语种	英语
DOI	10.3233/JAD-190158
发表期刊	JOURNAL OF ALZHEIMERS DISEASE
ISSN	1387-2877
卷号	71 期号:1 页码:291-305
收录类别	SCI ; SCI
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]
出版者	IOS PRESS
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
WOS类目	Neurosciences
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
引用统计	被引频次：24[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.psych.ac.cn/handle/311026/29837
专题	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
第一作者单位	脑与认知科学国家重点实验室
通讯作者单位	脑与认知科学国家重点实验室
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.