Molecular "negativity" may underlie multiple sclerosis: role of the myelin basic protein family in the pathogenesis of MS

Int Rev Neurobiol. 2007:79:149-72. doi: 10.1016/S0074-7742(07)79007-4.

Abstract

Myelin basic protein (MBP) binds to negatively charged lipids on the cytosolic surface of oligodendrocyte membranes and is responsible for adhesion of these surfaces in the multilayered myelin sheath. The pattern of extensive posttranslational modifications of MBP is dynamic during normal central nervous system development and during myelin degeneration in multiple sclerosis (MS), affecting its interactions with the myelin membranes and other proteins. In particular, the degree of deimination (or citrullination) of MBP is correlated with the severity of MS, and may represent a primary defect that precedes neurodegeneration due to autoimmune attack. That MBP deimination also affects topological accessibility of an otherwise partially buried immunodominant epitope of the protein indicates that this modification may play a major role in the autoimmune pathogenesis of the disease. In this chapter, we describe the structural and functional consequences of MBP deimination in healthy and diseased myelin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmunity
  • Demyelinating Diseases
  • Humans
  • Immunodominant Epitopes
  • Multiple Sclerosis / etiology*
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / metabolism*
  • Multiple Sclerosis / pathology
  • Myelin Basic Protein / classification
  • Myelin Basic Protein / immunology
  • Myelin Basic Protein / metabolism*
  • Myelin Sheath / immunology
  • Myelin Sheath / metabolism
  • Myelin Sheath / pathology
  • Protein Conformation
  • Protein Processing, Post-Translational

Substances

  • Immunodominant Epitopes
  • Myelin Basic Protein