Biochemistry and Molecular Mechanism Laboratory, Agro-Processing and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, 695019, Kerala, India.
Inflammopharmacology. 2020 Dec;28(6):1457-1476. doi: 10.1007/s10787-020-00757-9. Epub 2020 Sep 18.
Rheumatoid arthritis (RA), a multifactorial disease characterized by synovitis, cartilage destruction, bone erosion, and periarticular decalcification, finally results in impairment of joint function. Both genetic and environmental factors are risk factors in the development of RA. Unwanted side effects accompany most of the current treatment strategies, and around 20-40% of patients with RA do not clinically benefit from these treatments. The unmet need for new treatment options for RA has prompted research in the development of novel agents acting through physiologically and pharmacologically relevant targets. Here we discuss in detail three critical pathways, Janus kinase/signal transducer and activator of transcription (JAK/STAT), Th17, and hypoxia-inducible factor (HIF), and their roles as unique therapeutic targets in the field of RA. Some of the less developed but potential targets like nucleotide-binding and oligomerization domain-like receptor containing protein 3 (NLRP3) inflammasome and histone deacetylase 1 (HDAC1) are also discussed.
类风湿关节炎（RA）是一种多因素疾病，其特征为滑膜炎、软骨破坏、骨侵蚀和关节周围脱钙，最终导致关节功能受损。遗传和环境因素都是 RA 发展的危险因素。目前大多数治疗策略都伴随着不良反应，大约 20-40%的 RA 患者对这些治疗方法没有临床获益。对 RA 新治疗方案的未满足需求促使人们研究开发通过生理和药理学相关靶点发挥作用的新型药物。在这里，我们详细讨论了三个关键途径，即 Janus 激酶/信号转导和转录激活因子（JAK/STAT）、Th17 和缺氧诱导因子（HIF），以及它们作为 RA 领域独特治疗靶点的作用。我们还讨论了一些不太发达但有潜力的靶点，如核苷酸结合寡聚化结构域样受体包含蛋白 3（NLRP3）炎性小体和组蛋白去乙酰化酶 1（HDAC1）。
