Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immunoreactivity to the free radical-related enzymes, nitric oxide synthase (NOS) and superoxide dismutase (SOD), was examined in brain tissue in progressive supranuclear palsy (PSP). To determine the relationship between the immunoexpression of these enzymes and tau-positive, argyrophilic cytoplasmic inclusions, which are constantly present in PSP brains, double-label immunohistochemistry was applied. We demonstrated for the first time that strong inducible NOS-like immunoreactivity (iNOS-ir) was detected in tau-positive astrocytes that bore tufts of abnormal fibers (TAF), but not in oligodendrocytes containing argyrophilic/tau-positive coiled bodies nor in microglia. No brain NOS-ir was detected in neurons with neurofibrillary tangles. MnSOD-ir was also detected in tau-positive astrocytes and oligodendrocytes. Nitrotyrosine-ir of variable intensity was observed in astrocytes, oligodendrocytes and neurons. Our results indicate: (1) that TAF-bearing astrocytes may be a major source of excessive NO in PSP brains; (2) that after the induction of iNOS by unknown stimulating factors, TAF-bearing astrocytes produce an excessive amount of NO that exceeds the detoxification capability of SOD; and (3) that peroxynitrite and excessive NO, both cytotoxic, may be present in astrocytes, oligodendrocytes and neurons. Although the precise relationship between NO production and neuronal cell death in PSP remained uncertain, based on the specificity of TAF for PSP brains, our results indicated a possible mechanism of NO-mediated cytotoxicity that may contribute to the neuronal and glial cell damage followed by abnormal tau accumulation in this disease.
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PMID:Inducible nitric oxide synthase (iNOS)-like immunoreactivity in argyrophilic, tau-positive astrocytes in progressive supranuclear palsy. 956 10

Recent evidence implicates oxidative stress in the pathophysiology of progressive supranuclear palsy (PSP). Thus, we undertook a study of the activity and localization of two essential antioxidant systems (superoxide dismutase [SOD] enzymes and total glutathione) in the human post-mortem PSP and control brain. Marked increases in SOD1 (Cu/ZnSOD) activity and glutathione levels were measured within most PSP brain regions examined, whereas, only the subthalamic nucleus exhibited a significant increase (+68%) in SOD2 (MnSOD) activity. Two additional cases with mild pathological abnormalities were studied. The first (case A) may represent an example of an asymptomatic PSP case, while the second (case B) had mild pathological abnormalities consistent with typical PSP. In case A, only the STN had elevated levels of SOD activity, in the absence of an increase in tissue glutathione content. In case B, SOD activities and tissue glutathione content were elevated in several regions. Immunolocalization of the SOD1 and SOD2 proteins in paraffin-embedded tissue sections revealed a marked increase in the density of SOD immunopositive profiles (particularly glia) in the typical PSP brain, particularly within the white matter. Together, our data argues strongly in favor of the involvement of oxidative stress in the etiology and progression of PSP, and suggests that deficit in SOD or glutathione metabolism are not causative.
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PMID:Expression and activity of antioxidants in the brain in progressive supranuclear palsy. 1187 7