Microglial inflammation in the parkinsonian substantia nigra: relationship to alpha-synuclein deposition
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Background: The role of both microglial activation and alpha-synuclein deposition in Parkinson's disease remain unclear. We have tested the hypothesis that if microglia play a primary role in Parkinson's disease pathogenesis, the microglial "activated" phenotype should be associated with histopathological and/or clinical features of the disease. Methods: We have examined microglial MHC class II expression, a widely used marker of microglial activation, the occurrence of CD68-positive phagocytes and alpha-synuclein immunoreactivity in post-mortem human substantia nigra affected by idiopathic Parkinson's disease (PD). Using semi-quantitative severity ratings, we have examined the relationship between microglial activation, alpha-synuclein deposition, classical neuropathological criteria for PD, subtype of the disease and clinical course. Results: While we did not observe an association between microglial MHC class II expression and clinical parameters, we did find a correlation between disease duration and the macrophage marker CD68 which is expressed by phagocytic microglia. In addition, we observed a significant correlation between the degree of MHC class II expression and alpha-synuclein deposition in the substantia nigra in PD. Conclusion: While microglia appeared to respond to alpha-synuclein deposition, MHC class II antigen expression by microglia in the substantia nigra cannot be used as an indicator of clinical PD severity or disease progression. In addition, a contributory or even causative role for microglia in the neuronal loss associated with PD as suggested by some authors seems unlikely. Our data further suggest that an assessment of microglial activation in the aged brain on the basis of immunohistochemistry for MHC class II antigens alone should be done with caution.
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Microglia accumulate near α-synuclein deposits and become proinflammatory via receptors that also bind Aβ, such as CD36 and TLR2.
“Microglia accumulate near α-synuclein deposits and become proinflammatory in a manner dependent on receptors that also bind Aβ, such as CD36 and TLR263–65.”
From Microglia in neurodegeneration (2018) · cites this paper as [63]
Microglia phagocytose α-synuclein and become pro-inflammatory, expressing cytokines (IL1β, IL6, TNFα), ROS and COX2.
“Microglia also phagocytose α-synuclein, the constituent protein of Lewy bodies in Parkinson’s and Lewy Body dementias, and become pro-inflammatory in the process, expressing cytokines (IL1β, IL6, TNFα), reactive oxygen species (ROS) and prostaglandin synthesising cyclooxygenase 2 (COX2) [24,25,26].”
From ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease (2020) · cites this paper as [24]
Dysregulation of microglia functions contributes to the pathogenesis of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and Huntington's disease.
“Dysregulation of microglia functions contribute to the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD) (6–8), Parkinson’s disease (PD) (9–12) and Huntington’s disease (HD) (13–15).”
From An environment-dependent transcriptional network specifies human microglia identity (2017) · cites this paper as [10]
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- Authors
- Croisier, E., Moran, L. B., Dexter, D. T., Pearce, R. K., & Graeber, M. B.
- Affiliations
- Imperial College London (GB)
- Corresponding author
- Graeber, Manuel B
- ORCID
- Dexter, David T
- Venue
- Journal of Neuroinflammation
- Published
- 2005-06-03
- Volume
- 2
- Issue
- 1
- Pages
- 14-14
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC1177985
- OpenAlex
- W1822935226
- Cited by
- 414
- References
- 34
- Citations by year
- 2026: 15 · 2025: 18 · 2024: 44 · 2023: 24 · 2022: 25 · 2021: 38 · 2020: 44 · 2019: 18 · 2018: 22 · 2017: 15 · 2016: 13 · 2015: 19 · 2014: 18 · 2013: 19 · 2012: 11
- FWCI
- 7.36
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Journal of Neuroinflammation (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Parkinson's UK (G-4028)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, microglial activation, substantia nigra, MHC class II expression, CD68, microglial phagocytosis, neuroinflammation, disease duration, neuronal loss, postmortem brain
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