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

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...

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Bibliographic Details
Published in:Molecular and cellular neuroscience 2000-12, Vol.16 (6), p.724-739
Main Authors: Knott, C., Stern, G., Wilkin, G.P.
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Annexin A1 - metabolism
Astrocytes - enzymology
Astrocytes - pathology
Cyclooxygenase 1
Cyclooxygenase 2
Encephalitis - enzymology
Encephalitis - pathology
Encephalitis - physiopathology
Female
Humans
Isoenzymes - metabolism
lipocortin 1
Male
Membrane Proteins
Microglia - enzymology
Microglia - pathology
Neostriatum - enzymology
Neostriatum - pathology
Neostriatum - physiopathology
Nerve Degeneration - enzymology
Nerve Degeneration - pathology
Nerve Degeneration - physiopathology
Neurons - enzymology
Neurons - pathology
Nitric Oxide Synthase - metabolism
Parkinson Disease - enzymology
Parkinson Disease - pathology
Parkinson Disease - physiopathology
Prostaglandin-Endoperoxide Synthases - metabolism
Prostaglandins - metabolism
Substantia Nigra - enzymology
Substantia Nigra - pathology
Substantia Nigra - physiopathology
Up-Regulation - physiology
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Summary: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.
ISSN:1044-7431
1095-9327
DOI:10.1006/mcne.2000.0914