2. Academic Validation
  3. Peli1 controls the survival of dopaminergic neurons through modulating microglia-mediated neuroinflammation

Peli1 controls the survival of dopaminergic neurons through modulating microglia-mediated neuroinflammation

  • Sci Rep. 2019 May 29;9(1):8034. doi: 10.1038/s41598-019-44573-w.
Dongfang Dai 1,  Jia Yuan 2,  Yan Wang 2,  Jing Xu 2,  Chaoming Mao 3,  Yichuan Xiao 4 5
Affiliations

Affiliations

  • 1 Department of Nuclear Medicine and Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, China.
  • 2 CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • 3 Department of Nuclear Medicine and Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, China. mcm20040901@126.com.
  • 4 Department of Nuclear Medicine and Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, China. ycxiao@sibs.ac.cn.
  • 5 CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China. ycxiao@sibs.ac.cn.
PMID: 31142803 DOI: 10.1038/s41598-019-44573-w
Abstract

Chronic neuroinflammation is known to contributes to the toxicity of neurodegeneration of Parkinson's disease (PD). However, the molecular and cellular mechanisms controlling inflammatory responses in the central nervous system remain poorly understood. Here we found that a E3 ubiquitin ligase Peli1 is dramatically induced only in the substantia nigra (SN) of the human and mouse PD brains. The ablation of Peli1 significantly suppressed LPS-induced production of neurotoxic mediators and proinflammatory cytokines in SN and in primary microglia, whereas Peli1 is dispensable for the inflammatory responses in astrocyte. Accordingly, Peli1 deficiency markedly inhibited neuron death induced by the conditioned medium from LPS-stimulated microglia. Mechanistical study suggested that Peli1 acts as a positive regulator of inflammatory response in microglia through activation of NF-κB and MAP kinase. Our results established Peli1 as a critical mediator in the regulation of microglial activation and neuroinflammation-induced death of dopaminergic neurons during PD pathogenesis, suggesting that targeting Peli1 may have therapeutic effect in neuroinflammation.

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