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Nox2 dependent redox-regulation of microglial response to amyloid-β stimulation and microgliosis in aging
Microglia express constitutively a Nox2 enzyme that is involved in neuroinflammation by the generation of reactive oxygen species (ROS). Amyloid β (Aβ) plays a crucial role in Alzheimer’s disease. However, the mechanism of Aβ-induced microglial dysfunction and redox-regulation of microgliosis in agi...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994719/ https://www.ncbi.nlm.nih.gov/pubmed/32005915 http://dx.doi.org/10.1038/s41598-020-58422-8 |
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author | Geng, Li Fan, Lampson M. Liu, Fangfei Smith, Colin Li, Jian -Mei |
author_facet | Geng, Li Fan, Lampson M. Liu, Fangfei Smith, Colin Li, Jian -Mei |
author_sort | Geng, Li |
collection | PubMed |
description | Microglia express constitutively a Nox2 enzyme that is involved in neuroinflammation by the generation of reactive oxygen species (ROS). Amyloid β (Aβ) plays a crucial role in Alzheimer’s disease. However, the mechanism of Aβ-induced microglial dysfunction and redox-regulation of microgliosis in aging remains unclear. In this study, we examined Nox2-derived ROS in mediating microglial response to Aβ peptide 1–42 (Aβ(42)) stimulation in vitro, in aging-associated microgliosis in vivo and in post-mortem human samples. Compared to controls, Aβ(42) markedly induced BV2 cell ROS production, Nox2 expression, p47(phox) and ERK1/2 phosphorylation, cell proliferation and IL-1β secretion. All these changes could be inhibited to the control levels in the presence of Nox2 inhibitor or superoxide scavenger. Compared to young (3–4 months) controls, midbrain tissues from wild-type aging mice (20–22 months) had significantly higher levels of Nox2-derived ROS production, Aβ deposition, microgliosis and IL-1β production. However, these aging-related changes were reduced or absent in Nox2 knockout aging mice. Clinical significance of aging-associated Nox2 activation, microgliosis and IL-1β production was investigated using post-mortem midbrain tissues of humans at young (25–38 years) and old age (61–85 years). In conclusion, Nox2-dependent redox-signalling is crucial in microglial response to Aβ(42) stimulation and in aging-associated microgliosis and brain inflammation. |
format | Online Article Text |
id | pubmed-6994719 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-69947192020-02-06 Nox2 dependent redox-regulation of microglial response to amyloid-β stimulation and microgliosis in aging Geng, Li Fan, Lampson M. Liu, Fangfei Smith, Colin Li, Jian -Mei Sci Rep Article Microglia express constitutively a Nox2 enzyme that is involved in neuroinflammation by the generation of reactive oxygen species (ROS). Amyloid β (Aβ) plays a crucial role in Alzheimer’s disease. However, the mechanism of Aβ-induced microglial dysfunction and redox-regulation of microgliosis in aging remains unclear. In this study, we examined Nox2-derived ROS in mediating microglial response to Aβ peptide 1–42 (Aβ(42)) stimulation in vitro, in aging-associated microgliosis in vivo and in post-mortem human samples. Compared to controls, Aβ(42) markedly induced BV2 cell ROS production, Nox2 expression, p47(phox) and ERK1/2 phosphorylation, cell proliferation and IL-1β secretion. All these changes could be inhibited to the control levels in the presence of Nox2 inhibitor or superoxide scavenger. Compared to young (3–4 months) controls, midbrain tissues from wild-type aging mice (20–22 months) had significantly higher levels of Nox2-derived ROS production, Aβ deposition, microgliosis and IL-1β production. However, these aging-related changes were reduced or absent in Nox2 knockout aging mice. Clinical significance of aging-associated Nox2 activation, microgliosis and IL-1β production was investigated using post-mortem midbrain tissues of humans at young (25–38 years) and old age (61–85 years). In conclusion, Nox2-dependent redox-signalling is crucial in microglial response to Aβ(42) stimulation and in aging-associated microgliosis and brain inflammation. Nature Publishing Group UK 2020-01-31 /pmc/articles/PMC6994719/ /pubmed/32005915 http://dx.doi.org/10.1038/s41598-020-58422-8 Text en © The Author(s) 2020, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Geng, Li Fan, Lampson M. Liu, Fangfei Smith, Colin Li, Jian -Mei Nox2 dependent redox-regulation of microglial response to amyloid-β stimulation and microgliosis in aging |
title | Nox2 dependent redox-regulation of microglial response to amyloid-β stimulation and microgliosis in aging |
title_full | Nox2 dependent redox-regulation of microglial response to amyloid-β stimulation and microgliosis in aging |
title_fullStr | Nox2 dependent redox-regulation of microglial response to amyloid-β stimulation and microgliosis in aging |
title_full_unstemmed | Nox2 dependent redox-regulation of microglial response to amyloid-β stimulation and microgliosis in aging |
title_short | Nox2 dependent redox-regulation of microglial response to amyloid-β stimulation and microgliosis in aging |
title_sort | nox2 dependent redox-regulation of microglial response to amyloid-β stimulation and microgliosis in aging |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994719/ https://www.ncbi.nlm.nih.gov/pubmed/32005915 http://dx.doi.org/10.1038/s41598-020-58422-8 |
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