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

Abdiwahab A Musse1, George Harauz

  • 1Department of Molecular and Cellular Biology, Biophysics Interdepartmental Group, University of Guelph, Ontario N1G 2W1, Canada.

International Review of Neurobiology
|May 29, 2007
PubMed

Insights

Myelin basic protein (MBP) modifications, like deimination, impact myelin sheath structure and function. Deimination correlates with multiple sclerosis (MS) severity, potentially driving autoimmune pathogenesis.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Immunology

Background:

  • Myelin basic protein (MBP) is crucial for myelin sheath adhesion in the central nervous system.
  • Posttranslational modifications of MBP are dynamic during development and degeneration.
  • Deimination (citrullination) of MBP is linked to multiple sclerosis (MS) severity.

Purpose of the Study:

  • To describe the structural and functional consequences of MBP deimination.
  • To investigate the role of MBP deimination in healthy and diseased myelin.
  • To explore the potential role of deimination in the autoimmune pathogenesis of MS.

Main Methods:

  • The study focuses on analyzing the structural and functional changes associated with MBP deimination.
  • Investigates the impact of deimination on MBP's interaction with myelin membranes and other proteins.
  • Examines how deimination affects the accessibility of immunodominant epitopes.

Main Results:

  • MBP deimination alters its interactions with myelin membranes and associated proteins.
  • The degree of MBP deimination correlates with the severity of multiple sclerosis.
  • Deimination affects the topological accessibility of a key MBP epitope.

Conclusions:

  • MBP deimination has significant structural and functional consequences in myelin.
  • Deimination may represent a primary defect preceding neurodegeneration in MS.
  • MBP deimination plays a critical role in the autoimmune pathogenesis of multiple sclerosis.

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