Inflammatory Regulators in Parkinson's Disease: iNOS, Lipocortin-1, and Cyclooxygenases-1 and -2
Abstract
Degeneration of dopaminergic neurons and focal gliosis are pathological hallmarks of Parkinson's disease and although the brain is described as immune-privileged focal immune reactions surround failing nigral neurons. We examined the cellular distribution of pro- and anti-inflammatory molecules in human parkinsonian and neurologically normal substantia nigra and caudate-putamen postmortem. An up-regulation of nitric oxide synthase- and cyclo-oxygenase-1- and -2-containing amoeboid microglia was found in parkinsonian but not control nigra. Astroglia contained low levels of these molecules in both groups. Lipocortin-1-immunoreactive amoeboid microglia were present within the astrocytic envelope of neurons adjacent to or within glial scars in parkinsonian nigra only. Lipocortin-1 is known to have neuroprotective and anti-inflammatory properties. Up-regulation of nitric oxide synthase is generally associated with neurodestruction whereas prostaglandin synthesis may be either neurodestructive or protective. The balance of these molecules is likely to be decisive in determining neuronal survival or demise.
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Microglial activation markers such as iNOS, COX, and CD68 are upregulated in PD patients.
“Other microglial activation markers, such as pro-inflammatory enzymes like iNOS and COX211,212 and phagocytosis-associated marker CD68,213 were also upregulated in PD patients.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [212]
The beneficial effect of FMT on neuroinflammation is ascribed to GM modulating microglia and astrocyte activation in SN by regulating the TLR4/NF-κB pathway and reducing expression of GSK3β, iNOS and IL-1β.
“This beneficial effect should be ascribed to the ability of GM to modulate microglia and astrocyte activation in SN by regulating the TLR4/NF-κB pro-inflammatory pathway and reducing the expression of GSK3β, iNOS and IL-1β, which are implicated in PD pathogenesis and progression [469,470,471,472,478,479,480].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [478]
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- Authors
- Knott, C., Stern, G., & Wilkin, G. P.
- Affiliations
- Imperial College London (GB)
- University College London (GB)
- Corresponding author
- Knott, C.
- Venue
- Molecular and Cellular Neuroscience
- Publisher
- Elsevier BV
- Published
- 2000-12
- Volume
- 16
- Issue
- 6
- Pages
- 724-739
- ISSN
- 1044-7431 (ISSN-L)
- OpenAlex
- W2090409342
- Cited by
- 503
- References
- 121
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 6 · 2023: 18 · 2022: 25 · 2021: 20 · 2020: 21 · 2019: 24 · 2018: 20 · 2017: 19 · 2016: 28 · 2015: 24 · 2014: 27 · 2013: 25 · 2012: 25
- FWCI
- 8.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, nitric oxide synthase, annexin A1, cyclooxygenase-1, cyclooxygenase-2, amoeboid microglia, astrocytes, substantia nigra, caudate-putamen, dopaminergic neuron loss, gliosis, neuroinflammation, prostaglandin synthesis, neuroprotection
- MeSH terms
- Aged, Aged, 80 and over, Astrocytes, Encephalitis, Female, Humans, Isoenzymes, Male, Membrane Proteins, Nerve Degeneration, Neurons, Parkinson Disease, Prostaglandin-Endoperoxide Synthases, Prostaglandins, Substantia Nigra, Up-Regulation, Neostriatum, Annexin A1, Microglia, Nitric Oxide Synthase, Cyclooxygenase 1, Cyclooxygenase 2
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