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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
Corresponding AuthorWei, Yan(yanwei@ibp.ac.cn) ; He, Rongqiao(herq@ibp.ac.cn)
2019
Source PublicationJOURNAL OF ALZHEIMERS DISEASE
ISSN1387-2877
Volume71Issue:1Pages:291-305
AbstractAdvanced 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.
KeywordAdvanced glycation end products brain-derived neurotrophic factor GSK-3 beta oxidative stress ribosylation tau hyperphosphorylation
DOI10.3233/JAD-190158
Indexed BySCI ; SCI
Language英语
Funding OrganizationNational 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
Funding ProjectNational 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 Research AreaNeurosciences & Neurology
WOS SubjectNeurosciences
WOS IDWOS:000484216500023
PublisherIOS PRESS
WOS KeywordGROWTH-FACTOR EXPRESSION ; D-RIBOSE ; ALZHEIMERS-DISEASE ; PROTEIN ; MEMORY ; BDNF ; TERM ; HIPPOCAMPUS ; MECHANISM ; STRESS
Citation statistics
Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/29837
Collection脑与认知科学国家重点实验室
Corresponding AuthorWei, Yan; He, Rongqiao
Affiliation1.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
Recommended Citation
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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