Contributions
Abstract: EP1458
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 13 Experimental models
Background: Post-translational modifications (PTM) that decrease the positive charge of myelin basic protein (MBP) are implicated in myelin damage and multiple sclerosis (MS). The citrullination of the arginine residues on MBP has been identified as a potential cause.
Objective: To identify changes in lysine and arginine PTMs to MBP in spinal cord tissue and correlated these changes to neurological disability scoring as a marker for the degree of myelin damage.
Methods: Increases in lysine acetylation and methylation of MBP isolated obtained from an experimental autoimmune encephalomyelitis (EAE) animal model of MS were assessed by using a mass spectrometry assay.
Results and conclusion: We show lysine acetylation increases by two-fold on MBP during the peak inflammatory phase post-EAE induction. We also find that MBP mono- and dimethyl-lysine, as well as asymmetric dimethyl-arginine are significantly elevated at peak EAE disability. These findings suggest that lysine PTM of MBP may play a pivotal role in the neurological disability that is associated with MS. Histone deacetylase inhibitors have been previously shown to improve neurological disability. Here we show that treatment with trichostatin A significantly improves the neurological disability of EAE mice through some other mechanisms other than increasing acetylation.
Disclosure: The Authors declare no conflict of interest.
Abstract: EP1458
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 13 Experimental models
Background: Post-translational modifications (PTM) that decrease the positive charge of myelin basic protein (MBP) are implicated in myelin damage and multiple sclerosis (MS). The citrullination of the arginine residues on MBP has been identified as a potential cause.
Objective: To identify changes in lysine and arginine PTMs to MBP in spinal cord tissue and correlated these changes to neurological disability scoring as a marker for the degree of myelin damage.
Methods: Increases in lysine acetylation and methylation of MBP isolated obtained from an experimental autoimmune encephalomyelitis (EAE) animal model of MS were assessed by using a mass spectrometry assay.
Results and conclusion: We show lysine acetylation increases by two-fold on MBP during the peak inflammatory phase post-EAE induction. We also find that MBP mono- and dimethyl-lysine, as well as asymmetric dimethyl-arginine are significantly elevated at peak EAE disability. These findings suggest that lysine PTM of MBP may play a pivotal role in the neurological disability that is associated with MS. Histone deacetylase inhibitors have been previously shown to improve neurological disability. Here we show that treatment with trichostatin A significantly improves the neurological disability of EAE mice through some other mechanisms other than increasing acetylation.
Disclosure: The Authors declare no conflict of interest.