O-GlcNAc glycosylation is an intracellular post-translational modification that regulates the activity of proteins in a manner similar to phosphorylation. The addition and removal of the sugar is dynamic and highly regulated, and has been found on over a thousand proteins. The modification is highly enriched in the brain, and is found on proteins such as tau, amyloid beta, and many others implicated in neurodegenerative disease pathology. The current study aims to better define the role of O-GlcNAc in the brain, through a conditional knockout mouse model. The single O-GlcNAc transferase that is responsible for the addition of the modification was conditionally knocked out in the murine forebrain after neuronal development. The animals exhibit rapid neurodegeneration and have increases in hyperphosphoryalted Tau and amyloid beta, which are hallmarks of Alzheimer's disease. Current studies are aimed at better characterizing the degeneration and uncovering the mechanisms that produce this striking phenotype.

Investigating the role of O-GlcNAc in the brain: A conditional knockout mouse model

243rd National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.