Fig. 2.

Deimination pathway in the pathogenesis of demyelinating disease. Normal myelin is shown on the left. The promoter of the PAD 2 gene contains methylated cytosines (closed lollipops) along its CpG island, which regulates its transcription. Some MBPcit is made under normal conditions by the deimination of arginyl residues “C” on MBP. The amount of MBPcit is not enough to destabilize the bilayer. During demyelination, the promoter of PAD 2 is demethylated (open lollipops) at cytosines in the CpG island. This demethylated promoter increases transcription of PAD 2, which increases the amount of MBPcit in myelin with subsequent destabilization of the myelin. Degradation of myelin protein fragments, in particular MBPcit fragments, become available to sensitize T-cells in the periphery, initiating the immune response