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Targeting citrullination in autoimmunity: insights learned from preclinical mouse models
Ylke Bruggeman1, Fernanda M C Sodré1, Mijke Buitinga1,2,3
1Department of Chronic Diseases and Metabolism, Laboratory for Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium.
Expert Opinion on Therapeutic Targets
|April 26, 2021
Summary
Peptidylarginine deiminase (PAD) inhibitors show promise for treating autoimmune diseases by reducing inflammation. Isozyme-specific inhibitors may offer safer and more effective therapeutic strategies for conditions like rheumatoid arthritis.
Area of Science:
- Biochemistry
- Immunology
- Pharmacology
Background:
- Aberrant citrullination and peptidylarginine deiminase (PAD) activity are implicated in autoimmune diseases including rheumatoid arthritis, inflammatory bowel diseases, systemic lupus erythematosus, multiple sclerosis, and type 1 diabetes.
- Elevated PAD activity serves as a common factor in these conditions, highlighting PADs as potential therapeutic targets.
Purpose of the Study:
- To review advancements in the design and preclinical application of PAD inhibitors for autoimmune diseases.
- To evaluate the therapeutic potential of pan-PAD and isozyme-specific PAD inhibitors in mouse models of autoimmunity.
Main Methods:
- Literature search of PubMed.gov for studies from 1994 to 2021.
- Analysis of research on PAD inhibitors' efficacy and safety in preclinical autoimmune models.
Main Results:
- Pan-PAD inhibition demonstrated efficacy in ameliorating, reversing, and preventing autoimmune disease symptoms in preclinical models.
- Potential risks associated with broad PAD inhibition in biological processes could impede clinical translation.
Conclusions:
- While pan-PAD inhibition is a promising strategy, isozyme-specific inhibitors are likely to offer improved safety profiles and better clinical translation prospects.
- Targeting specific PAD isozymes could elucidate their distinct roles in disease pathology and reduce the risk of adverse effects.
