Augmentation of PRDX1-DOK3 interaction alleviates rheumatoid arthritis progression by suppressing plasma cell differentiation.

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

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Augmentation of PRDX1-DOK3 interaction alleviates rheumatoid arthritis progression by suppressing plasma cell differentiation.

Author: Wenzhen DANG ¹ ; Xiaomin WANG ² ; Huaying LI ³ ; Yixuan XU ⁴ ; Xinyu LI ¹ ; Siqi HUANG ⁴ ; Hongru TAO ¹ ; Xiao LI ¹ ; Yulin YANG ⁴ ; Lijiang XUAN ⁴ ; Weilie XIAO ⁵ ; Dean GUO ⁴ ; Hao ZHANG ⁴ ; Qiong WU ³ ; Jie ZHENG ⁴ ; Xiaoyan SHEN ⁶ ; Kaixian CHEN ⁴ ; Heng XU ⁴ ; Yuanyuan ZHANG ⁴ ; Cheng LUO ¹
Author Information

1. School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.
2. School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.
3. MegaRobo Technologies Co., Ltd., Beijing 100085, China.
4. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
5. Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Pharmacy and School of Chemical Science and Technology, Yunnan University, Kunming 650500, China.
6. Department of Pharmacology and the Key Laboratory of Smart Drug Delivery Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, China.
Publication Type:Journal Article
Keywords: DOK3; Degradation; Interaction; Molecular glue; PRDX1; Plasma cell; Rheumatoid arthritis; Salvianolic acid B
From: Acta Pharmaceutica Sinica B 2025;15(8):3997-4013
CountryChina
Language:English
Abstract: 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.