Inhibitory role of peroxiredoxin 2 in LRRK2 kinase activity induced cellular pathogenesis

被引：1

作者：

Yan, Kang ^{[1
]}

Zhang, Wenfeng ^{[1
]}

Han, Xu ^{[1
]}

Chang, Fei ^{[1
]}

Liu, Yongjian ^{[1
,2
]}

机构：

[1] Nanjing Med Univ, Sch Basic Med Sci, Jiangsu Key Lab Xenotransplantat, 101 Longmian Ave, Nanjing 211166, Jiangsu, Peoples R China

[2] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Sch Med, Pittsburgh, PA 15216 USA

来源：

JOURNAL OF BIOMEDICAL RESEARCH | 2020年 / 34卷 / 02期

关键词：

peroxiredoxin; 2; LRRK2; Parkinson's disease; DISEASE-ASSOCIATED MUTATIONS; OXIDATIVE STRESS; GTPASE ACTIVITY; PARKINSONS; EXPRESSION; SUBTYPES; BINDING; RAB29; PC12;

D O I：

10.7555/JBR.33.20190090

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

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.

引用

页码：103 / 113

页数：11