Selective inhibition of peptidyl-arginine deiminase (PAD): can it control multiple inflammatory disorders as a promising therapeutic strategy?

Peptidyl arginine deiminases (PADs) are a family of post-translational modification enzymes that irreversibly citrullinate (deiminate) arginine residues of protein and convert them to a non-classical amino acid citrulline in the presence of calcium ions. It has five isotypes, such as PAD1, PAD2, PAD3, PAD4, and PAD6, found in mammalian species. It has been suggested that increased PAD expression in various tissues contributes to the development of multiple inflammatory diseases, including rheumatoid arthritis (RA), cancer, diabetes, and neurological disorders. Elevation of PAD enzyme expression depends on several factors like rising intracellular Ca2+ levels, oxidative stress, and proinflammatory cytokines. PAD inhibitors originating from natural or synthetic sources can be used as a novel therapeutic approach concerning inflammatory disorders. Here, we review the pathological role of PAD in several inflammatory disorders, factors that trigger PAD expression, epigenetic role and finally, decipher the therapeutic approach of PAD inhibitors in multiple inflammatory disorders.

Automated summary

Peptidyl arginine deiminases (PADs) are enzymes that irreversibly citrullinate arginine residues of protein in the presence of calcium ions. Increased PAD expression has been linked to various inflammatory diseases. Factors such as intracellular calcium levels, oxidative stress, and proinflammatory cytokines contribute to the elevation of PAD enzyme expression. PAD inhibitors derived from natural or synthetic sources show promise as a novel therapeutic approach for inflammatory disorders. This review discusses the pathological role of PAD in inflammatory diseases, factors triggering PAD expression, epigenetic regulation, and the therapeutic potential of PAD inhibitors.