Protein modification in disease pathogenesis

Peptidylarginine deiminase (PAD), a key mediator of post-translational citrullination process, is known to be directly affected by Ca 2+ homeostasis and convert peptidylarginine to peptidylcitrulline (protein citrullination) in a Ca 2+ -dependent manner. PAD and its catalytic product, citrullinated proteins, have emerged as key molecules in various human diseases including multiple sclerosis, rheumatoid arthritis, and Alzheimer’s disease. Previously, we have demonstrated pathological characterization of PAD2 and citrullinated proteins in the brains from sporadic Creutzfeldt-Jakob disease patients (sCJD) and scrapie-infected mice, an animal model of prion disease. Using proteomic analysis, various candidates including cytoskeletal and energy metabolism-associated proteins such as vimentin, GFAP, myelin basic protein (MBP), enolases, and aldolases were identified in prion disease. Since the citrullinated antigens are proposed as disease markers, we developed new antibodies specific for citrullinated candidates, and we are currently evaluating these antibodies for the use of biomarkers in the diagnosis of neurodegenerative diseases including Alzheimer’s disease and prion diseases. Today, I will introduce about our interesting findings using newly developed antibodies specific for citrullinated proteins in disease pathogenesis. By extension, we believe that translational approaches to addressing PAD-mediated citrullination in aging and aging-related diseases may contribute to improve our understanding of the pathophysiology of age-related diseases and to develop diagnostic, prognostic, or therapeutic biomarkers (NRF-2016R1A2B4006529, HI16C1085 & HI16C0965).