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糖原合成酶激酶-3 抑制剂作为一种多靶点抗类风湿药物。

Glycogen synthase kinase-3 inhibitor as a multi-targeting anti-rheumatoid drug.

机构信息

Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.

出版信息

Biochem Pharmacol. 2019 Jul;165:207-213. doi: 10.1016/j.bcp.2019.02.020. Epub 2019 Feb 15.

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that causes swelling, bone erosion, and joint disorder. Patients with RA therefore suffer from pain and physiological disability, and have a decreased quality of life. During the progression of RA, many different types of cells and inflammatory factors influence each other with an important role. A better understanding of the pathology of RA should therefore lead to the development of effective anti-rheumatoid drugs, such as the anti-TNFα antibody. Glycogen synthase kinase-3 (GSK-3) is a cytoplasmic serine/threonine protein kinase that is involved in a large number of key cellular processes and is dysregulated in a wide variety of diseases, including inflammation and osteoporosis. The accumulated evidence has suggested that GSK-3 could be involved in multiple steps in the progression of RA. In the present review, the mechanisms of the pathogenesis of RA are summarized, and recent developments and potential new drugs targeting GSK-3 are discussed.

摘要

类风湿关节炎(RA)是一种慢性炎症性关节疾病,可导致肿胀、骨侵蚀和关节紊乱。因此,RA 患者会遭受疼痛和生理残疾,并降低生活质量。在 RA 的进展过程中,许多不同类型的细胞和炎症因子相互影响,具有重要作用。因此,对 RA 病理学的更好理解应该会导致开发出有效的抗风湿药物,例如抗 TNFα 抗体。糖原合酶激酶-3(GSK-3)是一种细胞质丝氨酸/苏氨酸蛋白激酶,参与大量关键细胞过程,在包括炎症和骨质疏松症在内的多种疾病中失调。越来越多的证据表明,GSK-3 可能参与 RA 进展的多个步骤。在本综述中,总结了 RA 发病机制的机制,并讨论了最近针对 GSK-3 的新进展和潜在新药。

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