The Dysregulation of OGT/OGA Cycle Mediates Tau and APP Neuropathology in Down Syndrome.

ABSTRACT: Protein O-GlcNAcylation is a nutrient-related post-translational modification that, since its discovery some 30 years ago, has been associated with the development of neurodegenerative diseases. As reported in Alzheimer's disease (AD), flaws in the cerebral glucose uptake translate into reduced hexosamine biosynthetic pathway flux and subsequently lead to aberrant protein O-GlcNAcylation. Notably, the reduction of O-GlcNAcylated proteins involves also tau and APP, thus promoting their aberrant phosphorylation in AD brain and the onset of AD pathological markers. Down syndrome (DS) individuals are characterized by the early development of AD by the age of 60 and, although the two conditions present the same pathological hallmarks and share the alteration of many molecular mechanisms driving

SUBMITTER: Zuliani I 

PROVIDER: S-EPMC8116370 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature