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TREM2 ameliorates neuroinflammatory response and cognitive impairment via PI3K/AKT/FoxO3a signaling pathway in Alzheimer’s disease mice
Triggering receptor expressed on myeloid cells 2 (TREM2) has been shown with a neuroprotective function against inflammation and neuronal injury in Alzheimer’s disease (AD). However, the TREM2 induced anti-inflammatory mechanism is still not well known. In this study it has been demonstrated that th...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655179/ https://www.ncbi.nlm.nih.gov/pubmed/33065553 http://dx.doi.org/10.18632/aging.104104 |
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author | Wang, Yaping Lin, Yan Wang, Linhan Zhan, Hongrui Luo, Xiaoting Zeng, Yanyan Wu, Wen Zhang, Xingmei Wang, Fang |
author_facet | Wang, Yaping Lin, Yan Wang, Linhan Zhan, Hongrui Luo, Xiaoting Zeng, Yanyan Wu, Wen Zhang, Xingmei Wang, Fang |
author_sort | Wang, Yaping |
collection | PubMed |
description | Triggering receptor expressed on myeloid cells 2 (TREM2) has been shown with a neuroprotective function against inflammation and neuronal injury in Alzheimer’s disease (AD). However, the TREM2 induced anti-inflammatory mechanism is still not well known. In this study it has been demonstrated that the expression of TREM2 was upregulated in hippocampus of 5xFAD mice, whereas TREM2 knock-out mediated by AAV significantly increased the levels of pro-inflammatory cytokines and aggravated cognitive defect. Additionally, FoxO3a, a downstream member of the PI3K/AKT pathway, could be activated by TREM2 defect via the PI3K/AKT signaling in 5xFAD mice. That suggests TREM2-induced protection is associated with the PI3K-FoxO3a axis. On the contrary, overexpression of TREM2 alleviated the LPS-induced inflammatory response and induced M2 phenotype microglia in vitro. This phenomenon can be abolished by applying the PI3K inhibitor LY294002, suggesting FoxO3a not only participates in TREM2-induced anti-inflammation response, but is also involved in regulating the phenotype of microglia. Taken together, our results show that the protective functions of TREM2, both in inflammatory response and cognitive impairment as well as in the decrease of M1 phenotype microglia, are related to PI3K/AKT/FoxO3a signaling pathway in AD mice. |
format | Online Article Text |
id | pubmed-7655179 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-76551792020-11-19 TREM2 ameliorates neuroinflammatory response and cognitive impairment via PI3K/AKT/FoxO3a signaling pathway in Alzheimer’s disease mice Wang, Yaping Lin, Yan Wang, Linhan Zhan, Hongrui Luo, Xiaoting Zeng, Yanyan Wu, Wen Zhang, Xingmei Wang, Fang Aging (Albany NY) Research Paper Triggering receptor expressed on myeloid cells 2 (TREM2) has been shown with a neuroprotective function against inflammation and neuronal injury in Alzheimer’s disease (AD). However, the TREM2 induced anti-inflammatory mechanism is still not well known. In this study it has been demonstrated that the expression of TREM2 was upregulated in hippocampus of 5xFAD mice, whereas TREM2 knock-out mediated by AAV significantly increased the levels of pro-inflammatory cytokines and aggravated cognitive defect. Additionally, FoxO3a, a downstream member of the PI3K/AKT pathway, could be activated by TREM2 defect via the PI3K/AKT signaling in 5xFAD mice. That suggests TREM2-induced protection is associated with the PI3K-FoxO3a axis. On the contrary, overexpression of TREM2 alleviated the LPS-induced inflammatory response and induced M2 phenotype microglia in vitro. This phenomenon can be abolished by applying the PI3K inhibitor LY294002, suggesting FoxO3a not only participates in TREM2-induced anti-inflammation response, but is also involved in regulating the phenotype of microglia. Taken together, our results show that the protective functions of TREM2, both in inflammatory response and cognitive impairment as well as in the decrease of M1 phenotype microglia, are related to PI3K/AKT/FoxO3a signaling pathway in AD mice. Impact Journals 2020-10-16 /pmc/articles/PMC7655179/ /pubmed/33065553 http://dx.doi.org/10.18632/aging.104104 Text en Copyright: © 2020 Wang et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Wang, Yaping Lin, Yan Wang, Linhan Zhan, Hongrui Luo, Xiaoting Zeng, Yanyan Wu, Wen Zhang, Xingmei Wang, Fang TREM2 ameliorates neuroinflammatory response and cognitive impairment via PI3K/AKT/FoxO3a signaling pathway in Alzheimer’s disease mice |
title | TREM2 ameliorates neuroinflammatory response and cognitive impairment via PI3K/AKT/FoxO3a signaling pathway in Alzheimer’s disease mice |
title_full | TREM2 ameliorates neuroinflammatory response and cognitive impairment via PI3K/AKT/FoxO3a signaling pathway in Alzheimer’s disease mice |
title_fullStr | TREM2 ameliorates neuroinflammatory response and cognitive impairment via PI3K/AKT/FoxO3a signaling pathway in Alzheimer’s disease mice |
title_full_unstemmed | TREM2 ameliorates neuroinflammatory response and cognitive impairment via PI3K/AKT/FoxO3a signaling pathway in Alzheimer’s disease mice |
title_short | TREM2 ameliorates neuroinflammatory response and cognitive impairment via PI3K/AKT/FoxO3a signaling pathway in Alzheimer’s disease mice |
title_sort | trem2 ameliorates neuroinflammatory response and cognitive impairment via pi3k/akt/foxo3a signaling pathway in alzheimer’s disease mice |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655179/ https://www.ncbi.nlm.nih.gov/pubmed/33065553 http://dx.doi.org/10.18632/aging.104104 |
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