Evidence for an imbalance between tau O-GlcNAcylation and phosphorylation in the hippocampus of a mouse model of Alzheimer's disease

Pharmacological Research : the Official Journal of the Italian Pharmacological Society
Eleonora GattaJérôme Mairesse

Abstract

Intracellular accumulation of hyperphosphorylated tau protein is linked to neuronal degeneration in Alzheimer's disease (AD). Mounting evidence suggests that tau phosphorylation and O-N-acetylglucosamine glycosylation (O-GlcNAcylation) are mutually exclusive post-translational modifications. O-GlcNAcylation depends on 3-5% of intracellular glucose that enters the hexosamine biosynthetic pathway. To our knowledge, the existence of an imbalance between tau phosphorylation and O-GlcNAcylation has not been reported in animal models of AD, as yet. Here, we used triple transgenic (3xTg-AD) mice at 12 months, an age at which hyperphosphorylated tau is already detected and associated with cognitive decline. In these mice, we showed that tau was hyperphosphorylated on both Ser396 and Thr205 in the hippocampus, and to a lower extent and exclusively on Thr205 in the frontal cortex. Tau O-GlcNAcylation, assessed in tau immunoprecipitates, was substantially reduced in the hippocampus of 3xTg-AD mice, with no changes in the frontal cortex or in the cerebellum. No changes in the expression of the three major enzymes involved in O-GlcNAcylation, i.e., glutamine fructose-6-phosphate amidotransferase, O-linked β-N-acetylglucosamine transferase, ...Continue Reading

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Citations

Oct 20, 2017·Journal of Neurochemistry·Ilhan AkanJohn A Hanover
Jan 11, 2019·The Journal of Biological Chemistry·Gerald W Hart
Dec 22, 2019·Chembiochem : a European Journal of Chemical Biology·Madhu RameshThimmaiah Govindaraju
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Apr 16, 2019·ACS Chemical Neuroscience·Philip RyanSantosh Rudrawar

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