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Science China Life Sciences

, Volume 60, Issue 2, pp 189–201 | Cite as

Presenilin 2 deficiency facilitates Aβ-induced neuroinflammation and injury by upregulating P2X7 expression

  • Juliang Qin
  • Xiaoyu Zhang
  • Ziqiang Wang
  • Jinju Li
  • Zhen Zhang
  • Liangcai Gao
  • Hua Ren
  • Min Qian
  • Bing Du
Research Paper

Abstract

Accumulating evidence suggests that β-amyloid (Aβ)-induced neuroinflammation plays a prominent and early role in Alzheimer’s disease (AD). In this study, we demonstrated that Presenilin 2 (PS2) deficiency facilitates Aβ-induced neuroinflammation and injury by upregulating P2X7 expression both in vitro and in vivo. PS2 knockout mice demonstrated increased cognitive impairments and cerebral injury. PS2 deficiency increased the expression of P2X7 both in neurons and microglial cells. Furthermore, extracellular ATP also increased in both Aβ-treated and untreated PS2 knockout microglial cells. Notably, Aβ-induced classical proinflammatory cytokines such as IL-1β, IL-1α and TNF-α were increased in PS2 knockout microglial cells, suggesting a potential role for PS2 in the regulation of neuroinflammation. The expression of P2X7 clearly increased in PS2 knockdown BV2 cells. Consistent with in vivo data, Aβ-induced IL-1β production was also clearly enhanced in PS2 knockdown BV2 cells. Additionally, expression of the transcription factor Sp1 was increased in PS2 knockdown cells. When we treated PS2 knockdown cells with the specific Sp1 inhibitor MIT, we observed that enhanced P2X7 expression was significantly rescued. Taken together, these data suggests that PS2 plays a protective role during Aβ-induced neuroinflammation and injury through down-regulation of P2X7 expression.

Keywords

Presenilin 2 P2X7 Alzheimer’s disease β-amyloid inflammation 

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Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (31470040, 31570896, 81172816, 81672811), Doctoral Fund of Ministry of Education of China (20130076110013), and Science and Technology Commission of Shanghai Municipality (15JC1401500).

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Copyright information

© Science in China Press and Springer-Verlag GmbH 2017

Authors and Affiliations

  • Juliang Qin
    • 1
  • Xiaoyu Zhang
    • 1
  • Ziqiang Wang
    • 1
  • Jinju Li
    • 1
  • Zhen Zhang
    • 1
  • Liangcai Gao
    • 1
  • Hua Ren
    • 1
  • Min Qian
    • 1
  • Bing Du
    • 1
  1. 1.Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghaiChina

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