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首页> 外文期刊>The European Journal of Neuroscience >Concurrent alterations of O-GlcNAcylation and phosphorylation of tau in mouse brains during fasting.
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Concurrent alterations of O-GlcNAcylation and phosphorylation of tau in mouse brains during fasting.

机译:禁食期间老鼠大脑中O-GlcNAcylation和tau磷酸化的同时变化。

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Impaired brain glucose uptake/metabolism precedes the symptoms of Alzheimer disease (AD) and is likely to play a role in the development of the disease, but the mechanism by which it contributes to AD is not understood. Because glucose uptake/metabolism regulates protein O-GlcNAcylation, and the latter modulates phosphorylation of tau inversely, we investigated, in fasting Kunming mice, whether impaired brain glucose uptake/metabolism causes abnormal hyperphosphorylation of tau and, consequently, facilitates the neurofibrillary degeneration of AD via down-regulation of tau O-GlcNAcylation. We found that fasting caused decreased tau O-GlcNAcylation and concurrent hyperphosphorylation of tau at most of the phosphorylation sites studied. The hippocampus was found more vulnerable to the tau alterations than the cerebral cortex, which is consistent with the fact that it is the hippocampus that is first affected in AD. Furthermore, hyperphosphorylation of tau induced by fasting was reversible in the brain after re-feeding. These findings provide a novel mechanism explaining how impaired brain glucose uptake/metabolism contributes to AD and suggest that it may be feasible to treat AD by reversing the abnormal hyperphosphorylation of tau at early stages of the disease.
机译:脑葡萄糖摄取/代谢受损先于阿尔茨海默病(AD)的症状,并可能在疾病的发展中起作用,但尚不清楚其促成AD的机制。因为葡萄糖摄取/代谢调节蛋白O-GlcNAcylation,而后者反过来调节tau的磷酸化,所以我们在禁食昆明小鼠中研究了脑葡萄糖摄取/代谢受损是否会导致tau异常过度磷酸化,从而促进AD的神经原纤维变性。通过下调tau O-GlcNAcylation。我们发现,禁食可导致大多数研究的磷酸化位点的tau O-GlcNAcylation降低和同时的tau过度磷酸化。发现海马比大脑皮层更容易遭受tau改变,这与在AD中首先感染海马的事实相符。此外,禁食诱导的tau过度磷酸化在重新喂食后在大脑中是可逆的。这些发现提供了一种新颖的机制来解释脑葡萄糖摄取/代谢受损如何导致AD,并表明通过逆转tau疾病早期的异常磷酸化过度来治疗AD是可行的。

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