Cited by 503Neuroinflammation and Neurodegeneration MechanismsParkinson's Disease Mechanisms and TreatmentsNuclear Receptors and Signaling

Inflammatory Regulators in Parkinson's Disease: iNOS, Lipocortin-1, and Cyclooxygenases-1 and -2

Knott, C., Stern, G., Wilkin, G.P.·2000·Molecular and Cellular Neuroscience

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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Registry

Crossref · 10.1006/mcne.2000.0914

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121 of 121 references verified0 citation errors · 0 not checkable

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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.”
  • 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].”

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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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