• Ya-Jie Ji, Hui-Lin Wang, Bian-Li Yin, and Xiang-Yang Ren.
• Department of Neurology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471009, Henan Province, PR China.
• Neuroscience. 2020 Aug 21; 442: 253-263.

AbstractMicroglia-mediated neuroinflammation plays a significant role in the pathogenesis of Parkinson's disease (PD). Down-regulation of DJ-1, a PD-associated protein, has been recently found to increase microglial sensitivity to lipopolysaccharides (LPS). However, the role of DJ-1 in microglia-mediated neuroinflammation in PD remains unclear. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to establish a PD model with mice and tyrosine hydroxylase (TH) staining was performed to validate the model. Adenovirus strategy and shRNA was employed to knockdown the expression of DJ-1 in mice and BV2 microglia, respectively. Western Blot and quantitative PCR were carried out to determine the expression of cytokines, DJ-1, Nrf2, Trx1 and NRLP3. Immunoprecipitation was used to examine the potential interaction between DJ-1 and Nrf2 or Trx1. Flow cytometry-based Annexin V/7-AAD assay were performed to evaluate cell apoptosis. We found that down-regulation of DJ-1 exacerbated neuroinflammation in PD mice. DJ-1 and Nrf2 knockdown promoted inflammation and cell apoptosis in BV2 microglia, while NLRP3 knockdown had opposite effects. Furthermore, DJ-1 regulated the expression of NLRP3 by upregulating Nrf2/Trx1 axis. Taken together, these data suggested that down-regulation of DJ-1 accelerated microglia-mediated neuroinflammation and cell apoptosis via Nrf2/Trx1/NLRP3 axis. Thus, our results demonstrated the important role of DJ-1 in PD pathogenesis and warranted further investigation of DJ-1 as a therapeutic target for PD.Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.

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