Reduced protein O-glycosylation in the nervous system of the mutant SOD1 transgenic mouse model of amyotrophic lateral sclerosis. 
In the neurodegenerative disease amyotrophic lateral sclerosis (ALS), a number of proteins have been found to be hyperphosphorylated, including neurofilament proteins (NFs).  In addition to protein phosphorylation, another important post-translational modification is O-glycosylation with β-N-acetylglucosamine residues (O-GlcNAc) and it has been found that O-GlcNAc can modify proteins competitively with protein phosphorylation, so that increased O-GlcNAc can reduce phosphorylation at specific sites.  We evaluated a transgenic mouse model of ALS that overexpresses mutant superoxide dismutase (mSOD) and found that O-GlcNAc immunoreactivity levels are decreased in spinal cord tissue from mSOD mice, compared to controls.  This reduction in O-GlcNAc levels is prominent in the motor neurons of spinal cord.  We find that inhibition of O-GlcNAcase (OGA), the enzyme catalyzing removal of O-GlcNAc, using the inhibitor NButGT for 3 days, resulted in increased O-GlcNAc levels in spinal cord, both in mSOD and control mice.  Furthermore, NButGT increased levels of O-GlcNAc modified NF-medium in spinal cords of control mice, but not in mSOD mice.  These observations suggest that the neurodegeneration found in mSOD mice is associated with a reduction of O-GlcNAc levels in neurons, including motor neurons.