Importance of research on peptidylarginine deiminase and citrullinated proteins in age-related disease.

Peptidylarginine deiminases (PAD) are a group of post-translational modification enzymes that citrullinate (deiminate) protein arginine residues in a calcium ion-dependent manner. Enzymatic citrullination abolishes positive charges of native protein molecules, inevitably causing significant alterations in their structure and functions. Citrullinated protein has an important physiological purpose; the formation of a cornified layer of skin that covers the human body. Despite this beneficial function, citrullinated protein also has a negative side, because this protein's accumulation in the brain is a possible cause of Alzheimer's disease. In the present review, we introduce PAD and their protein citrullination function, now considered critical for advancing research on aging and disease.