Brain Transcriptome Changes Associated With an Acute Increase of Protein O-GlcNAcylation and Implications for Neurodegenerative Disease.

Enhancing protein O-GlcNAcylation by pharmacological inhibition of the enzyme O-GlcNAcase (OGA) has been considered as a strategy to decrease tau and amyloid-beta phosphorylation, aggregation, and pathology in Alzheimer's disease (AD). There is still more to be learned about the impact of enhancing global protein O-GlcNAcylation, which is important for understanding the potential of using OGA inhibition to treat neurodegenerative diseases. In this study, we investigated the acute effect of pharmacologically increasing O-GlcNAc levels, using the OGA inhibitor Thiamet G (TG), in normal mouse brains.

The role of protein O-GlcNAcylation in diabetic cardiomyopathy.

It is well established that diabetes markedly increases the risk of multiple types of heart disease including heart failure. However, despite substantial improvements in the treatment of heart failure in recent decades the relative increased risk associated with diabetes remains unchanged. There is increasing appreciation of the importance of the post translational modification by O-linked-N-acetylglucosamine (O-GlcNAc) of serine and threonine residues on proteins in regulating cardiomyocyte function and mediating stress responses.

Acute increase of protein O-GlcNAcylation in mice leads to transcriptome changes in the brain opposite to what is observed in Alzheimer's Disease.

Enhancing protein O-GlcNAcylation by pharmacological inhibition of the enzyme O-GlcNAcase (OGA) is explored as a strategy to decrease tau and amyloid-beta phosphorylation, aggregation, and pathology in Alzheimer's disease (AD). There is still more to be learned about the impact of enhancing global protein O-GlcNAcylation, which is important for understanding the mechanistic path of using OGA inhibition to treat AD. In this study, we investigated the acute effect of pharmacologically increasing O-GlcNAc levels, using OGA inhibitor Thiamet G (TG), on normal mouse brains.

Impact of -GlcNAcylation elevation on mitophagy and glia in the dentate gyrus.

-GlcNAcylation is a dynamic and reversible protein post-translational modification of serine or threonine residues which modulates the activity of transcriptional and signaling pathways and controls cellular responses to metabolic and inflammatory stressors. We and others have shown that -GlcNAcylation has the potential to regulate autophagy and mitophagy to play a critical role in mitochondrial quality control, but this has not been assessed in the brain. This is important since mitochondrial dysfunction contributes to the development of neurodegenerative disease.

Duplicated and dilated ovarian vein with coexistence of persistent mesonephric artery.

During standard cadaveric dissection we encountered multiple vascular variations in the retroperitoneum: duplicated and dilated left ovarian vein with the coexistence of a persistent right mesonephric artery.