Koushik Sindhu, Joshi Nivedita, Nagaraju Shruthi, Mahmood Sameer, Mudeenahally Krishna, Padmavathy Ramya, Jegatheesan Sooriya Kumar, Mullangi Ramesh, Rajagopal Sriram
a Bioinformatics , Jubilant Biosys Ltd ., Bangalore , India.
Expert Opin Ther Targets. 2017 Apr;21(4):433-447. doi: 10.1080/14728222.2017.1294160. Epub 2017 Feb 22.
Peptidyl arginine deiminase 4 (PAD4) is an enzyme that plays an important role in gene expression, turning out genetic code into functional products in the body. It is involved in a key post translational modification, which involves the conversion of arginine to citrulline. It regulates various processes such as apoptosis, innate immunity and pluripotency, while its dysregulation has a great impact on the genesis of various diseases. Over the last few years PAD4 has emerged as a potential therapeutic target for the treatment of rheumatoid arthritis (RA). Areas covered: In this review, we discuss the basic structure and function of PAD4, along with the role of altered PAD4 activity in the onset of RA and other maladies. We also elucidate the role of PAD4 variants in etiology of RA among several ethnic groups and the current pre-clinical inhibitors to regulate PAD4. Expert opinion: Citrullination has a crucial role in RA and several other disorders. Since PAD4 is an initiator of the citrullination, it is an important therapeutic target for inflammatory diseases. Therefore, an in depth knowledge of the roles and activity of PAD4 is required to explore more effective ways to conquer PAD4 related ailments, especially RA.
肽基精氨酸脱亚氨酶4（PAD4）是一种在基因表达中起重要作用的酶，它能将遗传密码转化为体内的功能产物。它参与一种关键的翻译后修饰，即精氨酸向瓜氨酸的转化。它调节多种过程，如细胞凋亡、先天免疫和多能性，而其失调对各种疾病的发生有很大影响。在过去几年中，PAD4已成为治疗类风湿性关节炎（RA）的潜在治疗靶点。涵盖领域：在本综述中，我们讨论了PAD4的基本结构和功能，以及PAD4活性改变在RA和其他疾病发病中的作用。我们还阐明了PAD4变体在几个种族群体RA病因中的作用以及目前调节PAD4的临床前抑制剂。专家意见：瓜氨酸化在RA和其他几种疾病中起关键作用。由于PAD4是瓜氨酸化的启动者，它是炎症性疾病的重要治疗靶点。因此，需要深入了解PAD4的作用和活性，以探索更有效的方法来攻克与PAD4相关的疾病，尤其是RA。
