Proteomic identification of altered protein O-GlcNAcylation in a triple transgenic mouse model of Alzheimer's disease

Biochimica Et Biophysica Acta. Molecular Basis of Disease
Antonella TramutolaFabio Di Domenico

Abstract

PET scan analysis demonstrated the early reduction of cerebral glucose metabolism in Alzheimer disease (AD) patients that can make neurons vulnerable to damage via the alteration of the hexosamine biosynthetic pathway (HBP). Defective HBP leads to flawed protein O-GlcNAcylation coupled, by a mutual inverse relationship, with increased protein phosphorylation on Ser/Thr residues. Altered O-GlcNAcylation of Tau and APP have been reported in AD and is closely related with pathology onset and progression. In addition, type 2 diabetes patients show an altered O-GlcNAcylation/phosphorylation that might represent a link between metabolic defects and AD progression. Our study aimed to decipher the specific protein targets of altered O-GlcNAcylation in brain of 12-month-old 3×Tg-AD mice compared with age-matched non-Tg mice. Hence, we analysed the global O-GlcNAc levels, the levels and activity of OGT and OGA, the enzymes controlling its cycling and protein specific O-GlcNAc levels using a bi-dimensional electrophoresis (2DE) approach. Our data demonstrate the alteration of OGT and OGA activation coupled with the decrease of total O-GlcNAcylation levels. Data from proteomics analysis led to the identification of several proteins with re...Continue Reading

Citations

Oct 26, 2018·Expert Review of Neurotherapeutics·Fabio Di DomenicoAntonella Tramutola
Oct 16, 2019·Frontiers in Pharmacology·Tommaso CassanoSilvana Gaetani
Jan 3, 2020·Neuromolecular Medicine·Jinsu ParkDong-Gyu Jo
May 31, 2019·Frontiers in Neuroscience·Suraiya A Ansari, Bright Starling Emerald
Nov 12, 2019·Expert Review of Proteomics·Fabio Di DomenicoAntonella Tramutola
Oct 23, 2020·International Journal of Molecular Sciences·Vidyasagar Naik BukkeTommaso Cassano
Apr 4, 2021·Proteomes·Ankit P Jain, Gajanan Sathe
May 28, 2019·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Natalia Rodrigues MantuanoAdriane Regina Todeschini

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