Cargando…
Microglia Function in Alzheimer’s Disease
Contrary to early views, we now know that systemic inflammatory/immune responses transmit to the brain. The microglia, the resident “macrophages” of the brain’s innate immune system, are most responsive, and increasing evidence suggests that they enter a hyper-reactive state in neurodegenerative con...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Research Foundation
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277080/ https://www.ncbi.nlm.nih.gov/pubmed/22363284 http://dx.doi.org/10.3389/fphar.2012.00014 |
_version_ | 1782223462372212736 |
---|---|
author | Solito, Egle Sastre, Magdalena |
author_facet | Solito, Egle Sastre, Magdalena |
author_sort | Solito, Egle |
collection | PubMed |
description | Contrary to early views, we now know that systemic inflammatory/immune responses transmit to the brain. The microglia, the resident “macrophages” of the brain’s innate immune system, are most responsive, and increasing evidence suggests that they enter a hyper-reactive state in neurodegenerative conditions and aging. As sustained over-production of microglial pro-inflammatory mediators is neurotoxic, this raises great concern that systemic inflammation (that also escalates with aging) exacerbates or possibly triggers, neurological diseases (Alzheimer’s, prion, motoneuron disease). It is known that inflammation has an essential role in the progression of Alzheimer’s disease (AD), since amyloid-β (Aβ) is able to activate microglia, initiating an inflammatory response, which could have different consequences for neuronal survival. On one hand, microglia may delay the progression of AD by contributing to the clearance of Aβ, since they phagocyte Aβ and release enzymes responsible for Aβ degradation. Microglia also secrete growth factors and anti-inflammatory cytokines, which are neuroprotective. In addition, microglia removal of damaged cells is a very important step in the restoration of the normal brain environment, as if left such cells can become potent inflammatory stimuli, resulting in yet further tissue damage. On the other hand, as we age microglia become steadily less efficient at these processes, tending to become over-activated in response to stimulation and instigating too potent a reaction, which may cause neuronal damage in its own right. Therefore, it is critical to understand the state of activation of microglia in different AD stages to be able to determine the effect of potential anti-inflammatory therapies. We discuss here recent evidence supporting both the beneficial or detrimental performance of microglia in AD, and the attempt to find molecules/biomarkers for early diagnosis or therapeutic interventions. |
format | Online Article Text |
id | pubmed-3277080 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Frontiers Research Foundation |
record_format | MEDLINE/PubMed |
spelling | pubmed-32770802012-02-23 Microglia Function in Alzheimer’s Disease Solito, Egle Sastre, Magdalena Front Pharmacol Pharmacology Contrary to early views, we now know that systemic inflammatory/immune responses transmit to the brain. The microglia, the resident “macrophages” of the brain’s innate immune system, are most responsive, and increasing evidence suggests that they enter a hyper-reactive state in neurodegenerative conditions and aging. As sustained over-production of microglial pro-inflammatory mediators is neurotoxic, this raises great concern that systemic inflammation (that also escalates with aging) exacerbates or possibly triggers, neurological diseases (Alzheimer’s, prion, motoneuron disease). It is known that inflammation has an essential role in the progression of Alzheimer’s disease (AD), since amyloid-β (Aβ) is able to activate microglia, initiating an inflammatory response, which could have different consequences for neuronal survival. On one hand, microglia may delay the progression of AD by contributing to the clearance of Aβ, since they phagocyte Aβ and release enzymes responsible for Aβ degradation. Microglia also secrete growth factors and anti-inflammatory cytokines, which are neuroprotective. In addition, microglia removal of damaged cells is a very important step in the restoration of the normal brain environment, as if left such cells can become potent inflammatory stimuli, resulting in yet further tissue damage. On the other hand, as we age microglia become steadily less efficient at these processes, tending to become over-activated in response to stimulation and instigating too potent a reaction, which may cause neuronal damage in its own right. Therefore, it is critical to understand the state of activation of microglia in different AD stages to be able to determine the effect of potential anti-inflammatory therapies. We discuss here recent evidence supporting both the beneficial or detrimental performance of microglia in AD, and the attempt to find molecules/biomarkers for early diagnosis or therapeutic interventions. Frontiers Research Foundation 2012-02-10 /pmc/articles/PMC3277080/ /pubmed/22363284 http://dx.doi.org/10.3389/fphar.2012.00014 Text en Copyright © 2012 Solito and Sastre. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited. |
spellingShingle | Pharmacology Solito, Egle Sastre, Magdalena Microglia Function in Alzheimer’s Disease |
title | Microglia Function in Alzheimer’s Disease |
title_full | Microglia Function in Alzheimer’s Disease |
title_fullStr | Microglia Function in Alzheimer’s Disease |
title_full_unstemmed | Microglia Function in Alzheimer’s Disease |
title_short | Microglia Function in Alzheimer’s Disease |
title_sort | microglia function in alzheimer’s disease |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277080/ https://www.ncbi.nlm.nih.gov/pubmed/22363284 http://dx.doi.org/10.3389/fphar.2012.00014 |
work_keys_str_mv | AT solitoegle microgliafunctioninalzheimersdisease AT sastremagdalena microgliafunctioninalzheimersdisease |