Abstract |
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.
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Authors | Yan Wei, Chanshuai Han, Yujing Wang, Beibei Wu, Tao Su, Ying Liu, Rongqiao He |
Journal | Aging cell
(Aging Cell)
Vol. 14
Issue 5
Pg. 754-63
(Oct 2015)
ISSN: 1474-9726 [Electronic] England |
PMID | 26095350
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. |
Chemical References |
- CK59 compound
- Glycation End Products, Advanced
- Guanidines
- Mapt protein, mouse
- tau Proteins
- Ribose
- Calcium-Calmodulin-Dependent Protein Kinase Type 2
- Glucose
- Kinetin
- pimagedine
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Topics |
- Alzheimer Disease
(chemically induced, metabolism, prevention & control)
- Animals
- Calcium-Calmodulin-Dependent Protein Kinase Type 2
(metabolism)
- Cell Survival
(drug effects)
- Diabetes Mellitus, Type 2
(complications, metabolism)
- Dose-Response Relationship, Drug
- Enzyme Activation
(drug effects)
- Glucose
(administration & dosage)
- Glycation End Products, Advanced
(metabolism)
- Guanidines
(pharmacology)
- Injections, Intraperitoneal
- Kinetin
(pharmacology)
- Male
- Mice
- Mice, Inbred C57BL
- Phosphorylation
(drug effects)
- Ribose
(administration & dosage, pharmacology)
- Tumor Cells, Cultured
- tau Proteins
(metabolism)
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