Protein hypercitrullination in CNS demyelinating disease reversed by PAD inhibition

Abstract

Protein deimination (the conversion of peptide-bound arginine residues to citrulline) is a posttranslational modification which has important consequences for both protein structure and function. In this reaction shown in Fig. 11.1, the quanidino group of arginine is deiminated to citrulline. Each arginine deiminated is accompanied by the loss of positive charge, since citrulline is neutral. Thus, the deimination of several arginines in a protein results in large changes in total charge, causing major changes in protein structure and function. This will be abundantly demonstrated in this article, highlighting myelin basic protein (MBP) and its effects on myelin structure and stability. These devastating effects on myelin suggest a basic mechanism preceding demyelination in multiple sclerosis (MS), the most common neurological disease of humans, affecting about two million people worldwide.