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1. chinaXiv:201605.01517 [pdf]

Ribosylation triggering Alzheimer's disease-like Tau hyperphosphorylation via activation of CaMKII

Wei, Yan; Han, Chanshuai; Wang, Yujing; Wu, Beibei; Su, Tao; Liu, Ying; He, Rongqiao; Wang, Yujing; Wu, Beibei; Liu, Ying; He, Rongqiao
Subjects: Biology >> Biophysics >> Cell Biology

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.

submitted time 2016-05-12 Hits2314Downloads1383 Comment 0

2. chinaXiv:201605.01317 [pdf]

Gavage of D-Ribose induces A beta-like deposits, Tau hyperphosphorylation as well as memory loss and anxiety-like behavior in mice

Wu, Beibei; Wei, Yan; Wang, Yujing; Su, Tao; Liu, Ying; He, Rongqiao; He, Rongqiao; He, Rongqiao; Wu, Beibei; Wang, Yujing; Zhou, Lei
Subjects: Biology >> Biophysics >> Oncology

In addition to D-Glucose, D-Ribose is also abnormally elevated in the urine of type 2 diabetic patients, establishing a positive correlation between the concentration of uric D-Ribose and the severity of diabetes. Intraperitoneal injection of D-Ribose causes memory loss and brain inflammation in mice. To simulate a chronic progression of age-related cognitive impairment, we orally administered D-Ribose by gavage at both a low and high dose to 8 week-old male C57BL/6J mice daily for a total of 6 months, followed by behavioral, histological and biochemical analysis. We found that long-term oral administration of D-Ribose impairs spatial learning and memory, accompanied by anxiety-like behavior. Tau was hyperphosphorylated at AT8, S396, S214 and T181 in the brain. A beta-like deposition was also found in the hippocampus for the high dose group. D-Glucose-gavaged mice did not show significant memory loss and anxiety-like behavior under the same experimental conditions. These results demonstrate that a long-term oral administration of D-Ribose not only induces memory loss with anxiety-like behavior, but also elevates A beta-like deposition and Tau hyperphosphorylation, presenting D-Ribose-gavaged mouse as a model for agerelated cognitive impairment and diabetic encephalopathy.

submitted time 2016-05-11 Hits3218Downloads1123 Comment 0

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