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Ribosylation triggering Alzheimer's disease-like Tau hyperphosphorylation via activation of CaMKII
Wei, Yan1; Han, Chanshuai1; Wang, Yujing1,2; Wu, Beibei1,2; Su, Tao1; Liu, Ying1,3; He, Rongqiao1,4
2015-10-01
发表期刊AGING CELL
ISSN1474-9718
文章类型Article
卷号14期号:5页码:754-763
摘要Type 2 diabetes mellitus (T2DM) is regarded as one of the serious risk factors for age-related cognitive impairment; however, a causal link between these two diseases has so far not been established. It was recently discovered that, apart from high D-glucose levels, T2DM patients also display abnormally high concentrations of uric D-ribose. Here, we show for the first time that the administration of D-ribose, the most active glycator among monosaccharides, produces high levels of advanced glycation end products (AGEs) and, importantly, triggers hyperphosphorylation of Tau in the brain of C57BL/6 mouse and neuroblastoma N2a cells. However, the administration of D-glucose showed no significant changes in Tau phosphorylation under the same experimental conditions. Crucially, suppression of AGE formation using an AGEs inhibitor (aminoguanidine) effectively prevents hyperphosphorylation of Tau protein. Further study shows AGEs resulted from ribosylation activate calcium-/calmodulin-dependent protein kinase type II (CaMKII), a key kinase responsible for Tau hyperphosphorylation. These data suggest that there is indeed a mechanistic link between ribosylation and Tau hyperphosphorylation. Targeting ribosylation by inhibiting AGE formation may be a promising therapeutic strategy to prevent Alzheimer's disease-like Tau hyperphosphorylation and diabetic encephalopathies.
关键词hyperphosphorylation ribosylation Tau protein
收录类别SCI
语种英语
WOS记录号WOS:000360767200005
引用统计
文献类型期刊论文
条目标识符http://ir.psych.ac.cn/handle/311026/15228
专题脑与认知科学国家重点实验室
作者单位1.Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, Beijing 100101, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Capital Med Univ, Beijing Inst Brain Disorders, Alzheimers Dis Ctr, Beijing, Peoples R China
4.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing 100101, Peoples R China
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Wei, Yan,Han, Chanshuai,Wang, Yujing,et al. Ribosylation triggering Alzheimer's disease-like Tau hyperphosphorylation via activation of CaMKII[J]. AGING CELL,2015,14(5):754-763.
APA Wei, Yan.,Han, Chanshuai.,Wang, Yujing.,Wu, Beibei.,Su, Tao.,...&He, Rongqiao.(2015).Ribosylation triggering Alzheimer's disease-like Tau hyperphosphorylation via activation of CaMKII.AGING CELL,14(5),754-763.
MLA Wei, Yan,et al."Ribosylation triggering Alzheimer's disease-like Tau hyperphosphorylation via activation of CaMKII".AGING CELL 14.5(2015):754-763.
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