Peptidylarginine deiminases (PADs)-mediated post-translational citrullination 
processes play key roles in protein functions and structural stability through 
the conversion of arginine to citrulline in the presence of excessive calcium 
concentrations. In brain, PAD2 is abundantly expressed and can be involved in 
citrullination in disease. Recently, we have reported pathological 
characterization of PAD2 and citrullinated proteins in scrapie-infected mice, 
but the implication of protein citrullination in the pathophysiology in human 
prion disease is not clear. In the present study, we explored the molecular and 
biological involvement of PAD2 and the pathogenesis of citrullinated proteins in 
frontal cortex of patients with sporadic Creutzfeldt-Jakob disease (sCJD). We 
found increased expression of PAD2 in reactive astrocytes that also contained 
increased levels of citrullinated proteins. In addition, PAD activity was 
significantly elevated in patients with sCJD compared to controls. From 
two-dimensional gel electrophoresis and MALDI-TOF mass analysis, we found 
various citrullinated candidates, including cytoskeletal and energy 
metabolism-associated proteins such as vimentin, glial fibrillary acidic 
protein, enolase, and phosphoglycerate kinase. Based on these findings, our 
investigations suggest that PAD2 activation and aberrant citrullinated proteins 
could play a role in pathogenesis and have value as a marker for the postmortem 
classification of neurodegenerative diseases.