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Glia-Driven Neuroinflammation and Systemic Inflammation in Alzheimer’s Disease
The neuroinflammatory hypothesis of Alzheimer’s disease (AD) was proposed more than 30 years ago. The involvement of the two main types of glial cells microglia and astrocytes, in neuroinflammation, was suggested early on. In this review, we highlight that the exact contributions of reactive glia to...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Bentham Science Publishers
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686312/ https://www.ncbi.nlm.nih.gov/pubmed/33176652 http://dx.doi.org/10.2174/1570159X18666201111104509 |
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author | Hashioka, Sadayuki Wu, Zhou Klegeris, Andis |
author_facet | Hashioka, Sadayuki Wu, Zhou Klegeris, Andis |
author_sort | Hashioka, Sadayuki |
collection | PubMed |
description | The neuroinflammatory hypothesis of Alzheimer’s disease (AD) was proposed more than 30 years ago. The involvement of the two main types of glial cells microglia and astrocytes, in neuroinflammation, was suggested early on. In this review, we highlight that the exact contributions of reactive glia to AD pathogenesis remain difficult to define, likely due to the heterogeneity of glia populations and alterations in their activation states through the stages of AD progression. In the case of microglia, it is becoming apparent that both beneficially and adversely activated cell populations can be identified at various stages of AD, which could be selectively targeted to either limit their damaging actions or enhance beneficial functions. In the case of astrocytes, less information is available about potential subpopulations of reactive cells; it also remains elusive whether astrocytes contribute to the neuropathology of AD by mainly gaining neurotoxic functions or losing their ability to support neurons due to astrocyte damage. We identify L-type calcium channel blocker, nimodipine, as a candidate drug for AD, which potentially targets both astrocytes and microglia. It has already shown consistent beneficial effects in basic experimental and clinical studies. We also highlight the recent evidence linking peripheral inflammation and neuroinflammation. Several chronic systemic inflammatory diseases, such as obesity, type 2 diabetes mellitus, and periodontitis, can cause immune priming or adverse activation of glia, thus exacerbating neuroinflammation and increasing risk or facilitating the progression of AD. Therefore, reducing peripheral inflammation is a potentially effective strategy for lowering AD prevalence. |
format | Online Article Text |
id | pubmed-8686312 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Bentham Science Publishers |
record_format | MEDLINE/PubMed |
spelling | pubmed-86863122022-01-14 Glia-Driven Neuroinflammation and Systemic Inflammation in Alzheimer’s Disease Hashioka, Sadayuki Wu, Zhou Klegeris, Andis Curr Neuropharmacol Article The neuroinflammatory hypothesis of Alzheimer’s disease (AD) was proposed more than 30 years ago. The involvement of the two main types of glial cells microglia and astrocytes, in neuroinflammation, was suggested early on. In this review, we highlight that the exact contributions of reactive glia to AD pathogenesis remain difficult to define, likely due to the heterogeneity of glia populations and alterations in their activation states through the stages of AD progression. In the case of microglia, it is becoming apparent that both beneficially and adversely activated cell populations can be identified at various stages of AD, which could be selectively targeted to either limit their damaging actions or enhance beneficial functions. In the case of astrocytes, less information is available about potential subpopulations of reactive cells; it also remains elusive whether astrocytes contribute to the neuropathology of AD by mainly gaining neurotoxic functions or losing their ability to support neurons due to astrocyte damage. We identify L-type calcium channel blocker, nimodipine, as a candidate drug for AD, which potentially targets both astrocytes and microglia. It has already shown consistent beneficial effects in basic experimental and clinical studies. We also highlight the recent evidence linking peripheral inflammation and neuroinflammation. Several chronic systemic inflammatory diseases, such as obesity, type 2 diabetes mellitus, and periodontitis, can cause immune priming or adverse activation of glia, thus exacerbating neuroinflammation and increasing risk or facilitating the progression of AD. Therefore, reducing peripheral inflammation is a potentially effective strategy for lowering AD prevalence. Bentham Science Publishers 2021-06-23 2021-06-23 /pmc/articles/PMC8686312/ /pubmed/33176652 http://dx.doi.org/10.2174/1570159X18666201111104509 Text en © 2021 Bentham Science Publishers https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited. |
spellingShingle | Article Hashioka, Sadayuki Wu, Zhou Klegeris, Andis Glia-Driven Neuroinflammation and Systemic Inflammation in Alzheimer’s Disease |
title | Glia-Driven Neuroinflammation and Systemic Inflammation in Alzheimer’s Disease |
title_full | Glia-Driven Neuroinflammation and Systemic Inflammation in Alzheimer’s Disease |
title_fullStr | Glia-Driven Neuroinflammation and Systemic Inflammation in Alzheimer’s Disease |
title_full_unstemmed | Glia-Driven Neuroinflammation and Systemic Inflammation in Alzheimer’s Disease |
title_short | Glia-Driven Neuroinflammation and Systemic Inflammation in Alzheimer’s Disease |
title_sort | glia-driven neuroinflammation and systemic inflammation in alzheimer’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686312/ https://www.ncbi.nlm.nih.gov/pubmed/33176652 http://dx.doi.org/10.2174/1570159X18666201111104509 |
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