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Immunoproteasome Subunit Low Molecular Mass Peptide 2 (LMP2) Deficiency Ameliorates LPS/Aβ1-42-Induced Neuroinflammation

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A Correction to this article was published on 31 January 2024

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Abstract

Low molecular mass peptide 2 (LMP2) is the β1i subunit of immunoproteasome (iP) which plays a key role in neuroinflammatory responses, and inhibition of iP exhibits a high neuroprotective action against neurodegenerative diseases. Since neuroinflammation has been shown to be involved in the development and progression of Alzheimer’s disease (AD), the aim of this study was to evaluate the anti-inflammatory role of LMP2 deficiency in AD in vivo and in vitro. Here, we found that LMP2 was upregulated in the brains of 5 × FAD and APP/PS1 mice and increased with age in C57/BL6 mice. We showed that the lack of LMP2 significantly decreased NLRP3 expression and downstream cytokine release in microglia, resulting in partially blocking Aβ1-42- or LPS-induced inflammation in vivo and in vitro, which ameliorated cognitive deficits in aged rats and D-galactose + Aβ1-42-treated rats. These results suggest that LMP2 contributes to the regulation of LPS-or Aβ-driven innate immune responses by diminishing NLRP3 expression and clarify that inhibition of iP function may mediate the inflammatory-related cognitive phenotype.

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The data used or analyzed during this study are available on reasonable request from the corresponding author (lycmellisa@126.com).

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Acknowledgements

We are indebted to Mr. Longkun Zhu for the assistance in the preparation of the manuscript.

Funding

This work was supported by the grants from Fujian Natural Science Foundation (Grant No. 2018 J01836 to Yingchun Liu and Grant No. 2021J01679 to Li Li).

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Authors and Affiliations

  1. Key Laboratory of Stem Cell Engineering and Regenerative Medicine, Fujian Province University/School of Basic Medical Science, Fujian Medical University, Fuzhou City, 350122, Fujian Province, China

    Yueting Guo, Shiyi Wang, Hengce Zhang, Xiaoyang Chen, Zihan Huang & Yingchun Liu

  2. Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou City, 350122, Fujian Province, China

    Li Li

  3. Department of Cell Biology and Genetics of Basic Medical Sciences, Fujian Medical University, Fuzhou City, 350122, Fujian Province, China

    Li Li

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  1. Yueting Guo
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Yingchun Liu designed all studies; material preparation, data collection, and analysis were performed by Yueting Guo, Shiyi Wang, Li Li, Hengce Zhang, Xiaoyang Chen, and Zihan Huang. The first draft of the manuscript was written by Yueting Guo and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Guo, Y., Wang, S., Li, L. et al. Immunoproteasome Subunit Low Molecular Mass Peptide 2 (LMP2) Deficiency Ameliorates LPS/Aβ1-42-Induced Neuroinflammation. Mol Neurobiol 61, 28–41 (2024). https://doi.org/10.1007/s12035-023-03564-9

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