Localisation of citrullinated proteins in normal appearing white matter and lesions in the central nervous system in multiple sclerosis

Abstract

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease, considered to be autoimmune in origin. Post-translational modification of central nervous system proteins, including glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP), through citrullination of arginine residues, may lead to exposure of neoepitopes, triggering autoimmunity. Here we investigated the expression of citrullinated proteins in active MS lesions, MS normal appearing white matter and control brain white matter. We demonstrate increased citrullinated GFAP and MBP by immunohistochemistry and western blotting in areas of ongoing demyelination, suggesting a pivotal role for deimination of GFAP and MBP in MS pathogenesis MS.

Application of metabolomics in autoimmune diseases: Insight into biomarkers and pathology

“…Multiple sclerosis is a chronic immune-mediated demyelinating disorder of the CNS around the axons of the brain and spinal cord, which is one of the most frequent causes of disability in young adults (Wallin et al, 2000;Bradford et al, 2014). MS is difficult to diagnose because symptoms of multiple sclerosis may mimic those of many other nervous system problems and the long-term outcome of multiple sclerosis is difficult to predict.…”

Peptidylarginine Deiminases as Mediators of Microvesicular Release - Novel Therapeutic Interventions

“…In many cases where protein deimination has been associated with neurodegenerative diseases, including multiple sclerosis (MS) [126][127][128][129], AD and PD, studies have mainly focused on histological analysis of post mortem human samples. AD post mortem human brain samples display increased protein deimination [41-43; [130][131][132] and deiminated proteins are present in amyloid-containing areas in amyloid-precursor-protein / presenilin1 (APP+PSEN1) transgenic AD mouse models [31,133].…”

Nanomedicine in Central Nervous System (CNS) Disorders: A Present and Future Prospective

“…192 Modification of myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) triggers lesions in white matter 192 that causes MS. Advanced stage of MS causes demyelination and tissue damage due to oxidative stress are found higher in the patients. 193 Ultra sized cerium oxide nanoparticles declines oxidative stress and alleviates motor deficits in MS brain.…”