Reduced protein O-glycosylation in the nervous system of the mutant SOD1 transgenic mouse model of amyotrophic lateral sclerosis

NEUROSCIENCE LETTERS

卷:516

Article

Vocadlo, David J.¹  Krieger, Charles² 

[1] Simon Fraser Univ, Dept Chem, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada

[2] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada

关键词: O-glycosylation;    Phosphorylation;    O-GlcNAc;    Neurofilament;    NButGT;    Amyotrophic lateral sclerosis;   

DOI  :  10.1016/j.neulet.2012.04.018

来源: Elsevier

【 摘 要 】

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 beta-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 COCA), 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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

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