Abstract
Demyelinating diseases specifically multiple sclerosis (MS) present with detrimental neurological deficits that include impairment in visual function. MS has been associated with hyper-deimination of myelin basic protein isoform 5 (MBP) which positively correlates with an increase in MS severity. Deimination is a post-translational modification responsible for the conversion of protein bound arginine (positive charged) to protein bound citrulline (neutral charge). This modification has a direct effects on the tertiary structure of MBP, which significantly increases unfolding and susceptibility for proteolysis, generating immune reactive peptides. These peptides propagate the autoimmune response and are key component of MS pathogenesis. MS has also been documented to have deficiencies in phospholipids which are a major constituent of the cytosolic myelin membrane (side that interacts with MBP). Based on these key features we hypothesized that a) deficiencies of specific phospholipid species in the MS animal model (EAE) lead to differential complexation with MBP, b) restoring endogenous complexation can protect MBP against hyper-deimination and c) supplementation of deficient lipids in the optic nerve can improve visual function.