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TNFAIP1 Is Upregulated in APP/PS1 Mice and Promotes Apoptosis in SH-SY5Y Cells by Binding to RhoB

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Abstract

Alzheimer’s disease (AD) poses a significant threat to human life and health. The intraneuronal accumulation of β-amyloid (Aβ) plaques in the brains of AD patients results in neuronal cell death, which is a key factor that triggers multiple changes in the pathogenesis of AD. The inhibition of Aβ-induced neuronal cell death may potentially help in the intervention and treatment of AD. Our previous study reported that tumor necrosis factor α-induced protein 1 (TNFAIP1) is induced by and promotes Aβ25–35-induced neurotoxicity in mouse neuronal cells, but the roles and regulatory mechanisms of TNFAIP1 are still largely unknown. In this study, our experimental results show that TNFAIP1 and p-TNFAIP1 (phosphorylation of TNFAIP1 at Ser280) are overexpressed in the neurons of the cortex and hippocampus in the brains of APP/PS1 mice, and the transcription factor NF-κB is involved in the Aβ-induced upregulation of TNFAIP1. Moreover, our results suggest that TNFAIP1 contributes to the Aβ-induced reactive oxygen species (ROS) production, decreased mitochondrial membrane potential (∆Ψm), and neuronal cell death in human SH-SY5Y cells. We further revealed that Aβ increases the binding of TNFAIP1 to RhoB, and knockdown of RhoB attenuates the TNFAIP1-induced apoptosis of human SH-SY5Y cells. These data suggest that TNFAIP1 is closely associated with AD pathogenesis, and overexpression of TNFAIP1 in the neurons of the brains of AD patients plays a role in apoptosis, at least in part, via RhoB signaling.

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Data Availability

The data used to support the findings of this study are included within the article.

Abbreviations

AD:

Alzheimer’s disease

TNFAIP1:

Tumor necrosis factor α-induced protein 1

Aβ:

Amyloid beta

Co-IP:

Co-immunoprecipitation

siRNA:

Small interfering RNA

NC siRNA:

Negative control small interfering RNA

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Acknowledgments

The authors gratefully thank support from the ethical committee of Hunan Normal University.

Funding

This work was funded in part by the financial support from the China Natural Science Foundation (81601122, 81770389), Hunan Natural Science Foundation (2017JJ3205), the Scientific Research Fund of Hunan Provincial

Education Department (17B162), and Hunan Provincial Department of Health (2016044).

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Author notes

  1. Ye Xiao and Yadan Li equally contributed to this work

Authors and Affiliations

  1. Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha, 410081, Hunan, China

    Ye Xiao, Huihui Zhang, Xing Feng, Shishan Yuan & Ning Liu

  2. State Key Laboratory of Developmental Biology of Freshwater Fish, School of Life Sciences, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, School of Life Sciences, Hunan Normal University, Changsha, 410081, Hunan, China

    Ye Xiao, Chenxi Wei, Yu Xun, Shuanglin Xiang & Ning Liu

  3. Department of Environmental Science, Changsha Environmental Protection College, Changsha, Hunan, 410004, P.R. China

    Yadan Li & Liping Yang

  4. Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Yinghua Jiang

Authors
  1. Ye Xiao
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  2. Yadan Li
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  10. Shuanglin Xiang
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  11. Ning Liu
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Contributions

Ning Liu, Shishan Yuan, and Shuanglin Xiang designed the experiments; Ning Liu, Ye Xiao, Yadan Li, Yinghua Jiang, Huihui Zhang, Chenxi Wei, Yu Xun, and Xing Feng performed the experiments; Ning Liu, Shishan Yuan, and Shuanglin Xiang helped in data analysis and paper writing. All authors have read and approved the manuscript.

Corresponding authors

Correspondence to Shishan Yuan, Shuanglin Xiang or Ning Liu.

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All animal care protocols and experiments were reviewed and approved by the Ethics Committee of Hunan Normal University.

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Xiao, Y., Li, Y., Zhang, H. et al. TNFAIP1 Is Upregulated in APP/PS1 Mice and Promotes Apoptosis in SH-SY5Y Cells by Binding to RhoB. J Mol Neurosci 71, 1221–1233 (2021). https://doi.org/10.1007/s12031-020-01748-9

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