Inhibitory role of peroxiredoxin 2 in LRRK2 kinase activity induced cellular pathogenesis
Kang Yan1
Wenfeng Zhang1
Xu Han1
Fei Chang1
Yongjian Liu2
1.Jiangsu Key Laboratory of Xenotransplantation, School of Basic Medical Science, Nanjing Medical University,Nanjing, Jiangsu 211166, China2.Jiangsu Key Laboratory of Xenotransplantation, School of Basic Medical Science, Nanjing Medical University,Nanjing, Jiangsu 211166, China;Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15216, USA
摘要：Parkinson's disease (PD) is a major neurodegenerative disease.One of the known genetic contributors to PD pathogenesis is leucine-rich repeat kinase 2 (LRRK2) whose mutations with elevated kinase activity could lead to both familial and sporadic PD.However,how the pathogenic kinase activity of LRRK2 is regulated remains largely unclear.Here we report that peroxiredoxin 2 (Prx2) was identified as a novel interacting protein to LRRK2 with preferential expression in dopaminergic neurons over other Prx proteins.We also confirmed that Prx2 interacted with LRRK2 through its COR domain and its overexpression significantly decreased the kinase activity of mutant LRRK2.Functionally,overexpressed Prx2 rescued the transfected cells from LRRK2 mutant induced apoptotic processes.Importantly,overexpressed Prx2 reversed the altered subcellular distribution of cation-independent mannose 6-phosphate receptor (CI-M6PR) induced by PD-mutant LRRK2.Our results suggest that,by interacting with LRRK2,Prx2 may play an inhibitory role in the LRRK2 mediated cellular toxicity in PD by inhibiting its kinase activity.
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分类号：R742.5(神经病学与精神病学)
论文发表日期：2020-03-30
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：11( 103-113 )
英文信息