Immunoproteasome Subunit Low Molecular Mass Peptide 2 (LMP2) Deficiency Ameliorates LPS/$ Aβ_{1-42} $-Induced Neuroinflammation
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 $ Aβ_{1-42} $- or LPS-induced inflammation in vivo and in vitro, which ameliorated cognitive deficits in aged rats and D-galactose + $ Aβ_{1-42} $-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..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:61 |
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| Enthalten in: |
Molecular neurobiology - 61(2023), 1 vom: 12. Aug., Seite 28-41 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Guo, Yueting [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
Alzheimer’s disease |
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| Anmerkungen: |
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. corrected publication 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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| doi: |
10.1007/s12035-023-03564-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a 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 $ Aβ_{1-42} $- or LPS-induced inflammation in vivo and in vitro, which ameliorated cognitive deficits in aged rats and D-galactose + $ Aβ_{1-42} $-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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| 700 | 1 | |a Chen, Xiaoyang |4 aut | |
| 700 | 1 | |a Huang, Zihan |4 aut | |
| 700 | 1 | |a Liu, Yingchun |0 (orcid)0000-0002-3103-4997 |4 aut | |
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