Microglia in neurodegenerative disease
Microglia rapidly adopt an activated phenotype in response to brain injury and disease, which suggests that they could act as diagnostic markers of neurodegenerative disease onset or progression. In this article, Perry et al . review the relationship between activated microglia and neurodegenerative...
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| Published in: | Nature reviews. Neurology Vol. 6; no. 4; pp. 193 - 201 |
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| Main Authors: | , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
London
Nature Publishing Group UK
01-04-2010
Nature Publishing Group |
| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Microglia rapidly adopt an activated phenotype in response to brain injury and disease, which suggests that they could act as diagnostic markers of neurodegenerative disease onset or progression. In this article, Perry
et al
. review the relationship between activated microglia and neurodegenerative diseases and discuss the interactions between microglial phenotype, systemic inflammation and neurodegenerative disease progression.
Microglia, the resident macrophages of the CNS, are exquisitely sensitive to brain injury and disease, altering their morphology and phenotype to adopt a so-called activated state in response to pathophysiological brain insults. Morphologically activated microglia, like other tissue macrophages, exist as many different phenotypes, depending on the nature of the tissue injury. Microglial responsiveness to injury suggests that these cells have the potential to act as diagnostic markers of disease onset or progression, and could contribute to the outcome of neurodegenerative diseases. The persistence of activated microglia long after acute injury and in chronic disease suggests that these cells have an innate immune memory of tissue injury and degeneration. Microglial phenotype is also modified by systemic infection or inflammation. Evidence from some preclinical models shows that systemic manipulations can ameliorate disease progression, although data from other models indicates that systemic inflammation exacerbates disease progression. Systemic inflammation is associated with a decline in function in patients with chronic neurodegenerative disease, both acutely and in the long term. The fact that diseases with a chronic systemic inflammatory component are risk factors for Alzheimer disease implies that crosstalk occurs between systemic inflammation and microglia in the CNS.
Key Points
The phenotype of microglia is tightly regulated within the normal healthy CNS
Microglia rapidly change their morphology and expression of diverse molecules in response to changes in homeostasis and pathological insults to the brain
Morphologically activated microglia display diverse phenotypes that critically depend on the sequence and duration of their exposure to various stimuli in different pathologies
Microglial morphology and changes in expression of a small number of markers are not simple guides to microglial phenotype and function
Microglial phenotype is modified by systemic infection and inflammation
Systemic inflammation influences the symptoms and progression of chronic neurodegenerative disease |
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| Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 |
| ISSN: | 1759-4758 1759-4766 |
| DOI: | 10.1038/nrneurol.2010.17 |