témavezető: Nagy Tamás
helyszín (magyar oldal): PTE ÁOK Pécs, Szigeti u. 12. helyszín rövidítés: ÁOK
A kutatási téma leírása:
Protein O-linked N-acetylglucosamine modification (O-GlcNAc) is a reversible post-translational modification influenced by carbohydrate metabolism (its substrate is the end-product of the hexosamine pathway: UDP-GlcNAc). Elevated level of O-GlcNAc due to diabetes and its effects have been extensively studied, however O-GlcNAc’s role in hypoglycemic condition is less understood. Nevertheless, decreased O-GlcNAc has been implicated in the tau pathology of Alzheimer’s disease. Despite the fact that glucose metabolism significantly declines in the brain of Alzheimer’s patients, very few experimental evidence is presented so far that demonstrates a direct connection between deteriorated glucose metabolism and O-GlcNAc regulation. Thus, the objective of this study is to investigate the relationship between O-GlcNAc modification and Tau phosphorylation in a hypoglycemic model. First, we plan to establish a working cell culture model using SH-SY5Y neuroblastoma cells that mimics the low glucose availability of the Alzheimer’s neuron. Second, we will use this model to test whether protein O-GlcNAc modification is indeed decreased in these cells and whether tau-hyperphosphorylation is influenced by the altered O-GlcNAc state. Third, we will also test whether O-GlcNAc and tau phosphorylation could be reverted by adding alternative (e.g. beta-hydroxybutiric acid) nutritional sources to allow the cells to divert more glucose to the hexosamine pathway.
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