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 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.
Knott
C
C
Imperial College of Science, Technology and Medicine, Exhibition Road South, Kensington, London, SW7 2AZ, UK. c.knott.ic.ac.uk
Stern
G
G
Wilkin
G P
GP
D000368:Aged; D000369:Aged, 80 and over; D017305:Annexin A1 / Q000378:metabolism*; D001253:Astrocytes / Q000201:enzymology / Q000473:pathology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004660:Encephalitis / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D017628:Microglia / Q000201:enzymology / Q000473:pathology; D017072:Neostriatum / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D009410:Nerve Degeneration / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010300:Parkinson Disease / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D013378:Substantia Nigra / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D015854:Up-Regulation / Q000502:physiology*
D017305:Annexin A1; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D019001:Nitric Oxide Synthase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases