UNDERSTANDING THE ROLE OF PEPTIDYLARGININE DEIMINASES (PADs) IN DISEASES AND THEIR INHIBITORS AS POTENTIAL THERAPEUTIC AGENTS (REVIEW)
Sikander Ali*, Arshia Nazir, Sobia Shabbir and Shanza Ashraf
Proteins undergo post translational modifications (e.g. methylation, glycosylation, N-acetylation, phosphorylation and citrullination). Among these post-translational modifications is citrullination caused by peptidyl arginine deiminase (EC 18.104.22.168)family of enzymes that play an important role in maintaining homeostasis under normal physiological conditions. When dysregulated, PADs are involved in several diseases. This review describes the types, location, structure, mechanism, role of increased/overexpression of PADs in disease (RA, multiple sclerosis, ulcerative colitis, and CNS disorders and cancer). PADs inhibitors that serve as potential therapeutic agents are also discussed in this article review which include reversible and irreversible inhibitors with TDFA being the most potent selective inhibitor. Besides, some metals are also used as PADs inhibitors like zinc, samarium and manganese. These inhibitors proved to be very beneficial to control the diseases caused by the dysregulation of PADs.
Keywords: Peptidylarginine deiminases (PADs), Rheumatoid arthritis (RA), Central nervous system (CNS) and Threonine-aspartate-F-amidine (TDFA).
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