Citrullinated myelin basic protein (citMBP)

Citrullinated myelin basic protein (citMBP) is a post-translationally modified form of myelin basic protein, a primary structural component of the central nervous system myelin sheath. [1] This modification occurs when arginine residues are converted to citrulline by peptidyl arginine deiminase (PAD) enzymes, particularly PAD2 and PAD4. [2] In patients with multiple sclerosis (MS), the level of citMBP is significantly elevated, reaching up to 45% of total MBP compared to roughly 20% in healthy individuals. [3] The loss of positive charge during citrullination weakens the interaction between MBP and the lipid bilayer, leading to myelin destabilization and increased vulnerability to proteolytic enzymes. [2][3] Furthermore, citMBP acts as a potent autoantigen by presenting neoepitopes that are recognized by autoreactive T-cells, thereby driving the inflammatory cascade in MS. [4] Current therapeutic strategies focus on inhibiting PAD activity to prevent the formation of citMBP or using citrullinated peptides in antigen-specific immunotherapies to induce immune tolerance. [5] Consequently, citMBP is both a critical pathological mediator of demyelination and a high-value target for precision autoimmune therapies. [4] Sources: [1] Pritzker, L. B., et al. (2000). Journal of Biological Chemistry. [2] Moscarello, M. A., et al. (2007). Journal of Neurochemistry. [3] Wood, D. D., et al. (1996). Annals of Neurology. [4] Ireland, J. M., et al. (2012). Journal of Autoimmunity. [5] Kim, S. J., et al. (2021). Frontiers in Immunology.

Other names

Citrullinated MBPDeiminated myelin basic proteincit-MBPC8-MBP

Induction of immune tolerance to citrullinated neoepitopes or inhibition of peptidyl arginine deiminase (PAD) enzymes to prevent MBP citrullination.