- page settings
- showhide sidebar
- showhide empty fields
- layout
- (too narrow)
- open all
- close all
- Page Content
- Overview
- External Links
- History
- Referenced
- Tools
- Tree Display
- My WormBase
- My Favorites
- My Library
- Recent Activity
- Comments (0)
history logging is off
Tree Display
My Favorites
My Library
Comments on Wang, Peng et al. (2011) International Worm Meeting "Caenorhabditis elegans O-GlcNAc cycling mutants alter the proteotoxicity of models of human neurodegenerative disorders." (0)
Overview
Wang, Peng, Lazarus, Brooke, Forsythe, Michele, Love, Dona, Krause, Michael, & Hanover, John (2011). Caenorhabditis elegans O-GlcNAc cycling mutants alter the proteotoxicity of models of human neurodegenerative disorders presented in International Worm Meeting. Unpublished information; cite only with author permission.
O-linked N-acetylglucosamine (O-GlcNAc) addition is an important post-translational modification that occurs on hundreds of proteins, including nuclear pore proteins, transcription factors, proteasome components and neuronal proteins. O-GlcNAc can be added onto and removed from serine or threonine residue by two evolutionally conserved enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively. O-GlcNAcylation is abundant in the brain and it has been linked to human neurodegenerative disease. We have exploited viable null alleles of the enzymes of O-GlcNAc cycling to examine the role of O-GlcNAcylation in well-characterized C. elegans models of neurodegenerative proteotoxicity. O-GlcNAc cycling dramatically modulated the severity of the proteotoxic phenotype in transgenic models of tauopathy, b-amyloid peptide and polyglutamine expansion. Intriguingly, loss-of-function of OGT alleviated, while loss of OGA enhanced these proteotoxicity phenotype. Consistent with these observations, the O-GlcNAc cycling mutants exhibit altered stress responses and changes in the protein degradation machinery. These findings suggest that modulators of O-GlcNAc cycling may prove useful for anti-neurodegenerative disease therapies.
Affiliation:
- NIDDK, NIH, Bethesda, MD.