Padhy Dibya Sundar, Palit Partha, Ikbal Abu Md Ashif, Das Nirupam, Roy Dilip Kumar, Banerjee Sugato
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Kolkata, West Bengal, 700054, India.
Department of Pharmaceutical Sciences, Drug Discovery Research Laboratory, Assam University, Silchar, 788011, India.
Inflammopharmacology. 2023 Apr;31(2):731-744. doi: 10.1007/s10787-023-01149-5. Epub 2023 Feb 17.
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 Ca 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.
肽基精氨酸脱亚氨酶（PADs）是一类翻译后修饰酶，在钙离子存在的情况下，可将蛋白质的精氨酸残基不可逆地瓜氨酸化（脱亚氨基），并将其转化为一种非经典氨基酸——瓜氨酸。在哺乳动物物种中发现它有五种同种型，如PAD1、PAD2、PAD3、PAD4和PAD6。有人提出，各种组织中PAD表达的增加会导致多种炎症性疾病的发展，包括类风湿性关节炎（RA）、癌症、糖尿病和神经紊乱。PAD酶表达的升高取决于几个因素，如细胞内钙水平升高、氧化应激和促炎细胞因子。源自天然或合成来源的PAD抑制剂可作为一种针对炎症性疾病的新型治疗方法。在此，我们综述了PAD在几种炎症性疾病中的病理作用、触发PAD表达的因素、表观遗传作用，最后解读了PAD抑制剂在多种炎症性疾病中的治疗方法。
