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09:41
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Multiple sclerosis: an important role for post-translational modifications of myelin basic protein in pathogenesis
J K Kim1, F G Mastronardi, D D Wood
1Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055, USA.
Molecular & Cellular Proteomics : MCP
|July 2, 2003
Summary
Post-translational modifications of myelin basic protein (MBP) differ in multiple sclerosis (MS). Key changes in methylation, deimination, and phosphorylation suggest a role in demyelinating disease pathogenesis.
Area of Science:
- Neuroscience
- Biochemistry
- Immunology
Background:
- Myelin basic protein (MBP) is implicated as an autoantigen in multiple sclerosis (MS).
- Understanding post-translational modifications (PTMs) of MBP is crucial for elucidating MS pathogenesis.
Purpose of the Study:
- To compare PTMs of MBP in normal versus MS human white matter.
- To investigate the role of PTMs in demyelination using a mouse model.
Main Methods:
- Isolation and purification of MBP charge isomers from human white matter.
- Mass spectrometry analysis of tryptic peptides to quantify methylation, deimination, and phosphorylation.
- Western blot analysis using specific antibodies in a mouse model.
Main Results:
- Increased mono- and dimethylated arginine at position 107 in MS samples.
- Elevated deimination of arginine at multiple sites in MS samples.
- Significantly reduced phosphorylation of MBP peptides in MS samples compared to normal samples.
- Decreased phosphorylation and glycogen synthesis kinase in a mouse model of demyelination.
Conclusions:
- This study provides the first comprehensive analysis of PTMs in demyelinating diseases.
- Alterations in MBP PTMs, particularly reduced phosphorylation, are linked to MS pathogenesis.
- MBP PTMs represent potential therapeutic targets for demyelinating conditions.
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