Augmentation of PRDX1–DOK3 interaction alleviates rheumatoid arthritis progression by suppressing plasma cell differentiation
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can de...
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Elsevier
2025-08-01
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| Series: | Acta Pharmaceutica Sinica B |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383525004095 |
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| author | Wenzhen Dang Xiaomin Wang Huaying Li Yixuan Xu Xinyu Li Siqi Huang Hongru Tao Xiao Li Yulin Yang Lijiang Xuan Weilie Xiao Dean Guo Hao Zhang Qiong Wu Jie Zheng Xiaoyan Shen Kaixian Chen Heng Xu Yuanyuan Zhang Cheng Luo |
| author_facet | Wenzhen Dang Xiaomin Wang Huaying Li Yixuan Xu Xinyu Li Siqi Huang Hongru Tao Xiao Li Yulin Yang Lijiang Xuan Weilie Xiao Dean Guo Hao Zhang Qiong Wu Jie Zheng Xiaoyan Shen Kaixian Chen Heng Xu Yuanyuan Zhang Cheng Luo |
| author_sort | Wenzhen Dang |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy–lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1–DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases. |
| format | Article |
| id | doaj-art-51356e94a7774e9eb592d1a0e3bc24e1 |
| institution | Kabale University |
| issn | 2211-3835 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj-art-51356e94a7774e9eb592d1a0e3bc24e12025-08-20T05:06:36ZengElsevierActa Pharmaceutica Sinica B2211-38352025-08-011583997401310.1016/j.apsb.2025.06.006Augmentation of PRDX1–DOK3 interaction alleviates rheumatoid arthritis progression by suppressing plasma cell differentiationWenzhen Dang0Xiaomin Wang1Huaying Li2Yixuan Xu3Xinyu Li4Siqi Huang5Hongru Tao6Xiao Li7Yulin Yang8Lijiang Xuan9Weilie Xiao10Dean Guo11Hao Zhang12Qiong Wu13Jie Zheng14Xiaoyan Shen15Kaixian Chen16Heng Xu17Yuanyuan Zhang18Cheng Luo19School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaMegaRobo Technologies Co., Ltd., Beijing 100085, ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaSchool of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaSchool of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaSchool of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaKey Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Pharmacy and School of Chemical Science and Technology, Yunnan University, Kunming 650500, ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaMegaRobo Technologies Co., Ltd., Beijing 100085, ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaDepartment of Pharmacology and the Key Laboratory of Smart Drug Delivery Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding authors.State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding authors.School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; University of Chinese Academy of Sciences, Beijing 100049, China; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528437, China; Corresponding authors.Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy–lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1–DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.http://www.sciencedirect.com/science/article/pii/S2211383525004095Rheumatoid arthritisPlasma cellPRDX1DOK3DegradationInteraction |
| spellingShingle | Wenzhen Dang Xiaomin Wang Huaying Li Yixuan Xu Xinyu Li Siqi Huang Hongru Tao Xiao Li Yulin Yang Lijiang Xuan Weilie Xiao Dean Guo Hao Zhang Qiong Wu Jie Zheng Xiaoyan Shen Kaixian Chen Heng Xu Yuanyuan Zhang Cheng Luo Augmentation of PRDX1–DOK3 interaction alleviates rheumatoid arthritis progression by suppressing plasma cell differentiation Acta Pharmaceutica Sinica B Rheumatoid arthritis Plasma cell PRDX1 DOK3 Degradation Interaction |
| title | Augmentation of PRDX1–DOK3 interaction alleviates rheumatoid arthritis progression by suppressing plasma cell differentiation |
| title_full | Augmentation of PRDX1–DOK3 interaction alleviates rheumatoid arthritis progression by suppressing plasma cell differentiation |
| title_fullStr | Augmentation of PRDX1–DOK3 interaction alleviates rheumatoid arthritis progression by suppressing plasma cell differentiation |
| title_full_unstemmed | Augmentation of PRDX1–DOK3 interaction alleviates rheumatoid arthritis progression by suppressing plasma cell differentiation |
| title_short | Augmentation of PRDX1–DOK3 interaction alleviates rheumatoid arthritis progression by suppressing plasma cell differentiation |
| title_sort | augmentation of prdx1 dok3 interaction alleviates rheumatoid arthritis progression by suppressing plasma cell differentiation |
| topic | Rheumatoid arthritis Plasma cell PRDX1 DOK3 Degradation Interaction |
| url | http://www.sciencedirect.com/science/article/pii/S2211383525004095 |
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