1. Peptidylarginine deiminase (PAD): A promising target for chronic diseases treatment.
- Author
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Mansouri P, Mansouri P, Behmard E, Najafipour S, Kouhpayeh SA, and Farjadfar A
- Subjects
- Humans, Chronic Disease, Arthritis, Rheumatoid drug therapy, Arthritis, Rheumatoid enzymology, Protein-Arginine Deiminase Type 4 metabolism, Protein-Arginine Deiminase Type 4 antagonists & inhibitors, Protein-Arginine Deiminase Type 4 chemistry, Animals, Protein-Arginine Deiminase Type 2 chemistry, Protein-Arginine Deiminase Type 2 metabolism, Citrulline metabolism, Citrulline chemistry, Molecular Targeted Therapy, Protein-Arginine Deiminases metabolism, Protein-Arginine Deiminases antagonists & inhibitors, Protein-Arginine Deiminases chemistry, Enzyme Inhibitors chemistry, Enzyme Inhibitors pharmacology, Enzyme Inhibitors therapeutic use
- Abstract
In 1958, the presence of citrulline in the structure of the proteins was discovered for the first time. Several years later they found that Arginine converted to citrulline during a post-translational modification process by PAD enzyme. Each PAD is expressed in a certain tissue developing a series of diseases such as inflammation and cancers. Among these, PAD2 and PAD4 play a role in the development of rheumatoid arthritis (RA) by producing citrullinated autoantigens and increasing the production of inflammatory cytokines. PAD4 is also associated with the formation of NET structures and thrombosis. In the crystallographic structure, PAD has several calcium binding sites, and the active site of the enzyme consists of different amino acids. Various PAD inhibitors have been developed divided into pan-PAD and selective PAD inhibitors. F-amidine, Cl-amidine, and BB-Cl-amidine are some of pan-PAD inhibitors. AFM-30a and JBI589 are selective for PAD2 and PAD4, respectively. There is a need to evaluate the effectiveness of existing inhibitors more accurately in the coming years, as well as design and production of novel inhibitors targeting highly specific isoforms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)
- Published
- 2024
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