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)

Previous experimental data indicate the involvement of Ca(2+)-related excitotoxic processes, possibly mediated by N-Methyl-D-Aspartate (NMDA) receptors, in beta-amyloid (beta A) neurotoxicity. On the other hand, other lines of evidence support the view that free radical generation is a critical step in the beta A-induced neurodegenerative cascade. In the present study, therefore, a neuroprotective strategy was applied to explore the contributions of each of these pathways in beta A toxicity. beta A(1-42) was injected into the magnocellular nucleus basalis of rats, while neuroprotection was achieved by either single or combined administration of the NMDA receptor antagonist MK-801 (2.5 mg/kg) and/or a vitamin E and C complex (150 mg/kg). The degree of neurodegeneration was determined by testing the animals in consecutive series of behavioral tasks, including elevated plus maze, passive avoidance learning, small open-field and open-field paradigms, followed by acetylcholinesterase (AChE), choline-acetyltransferase (ChAT), and superoxide dismutase (SOD) biochemistry. beta A injected in the nucleus basalis elicited significant anxiety in the elevated plus maze, derangement of passive avoidance learning, and altered spontaneous behaviors in both open-field tasks. A significant decrease in both AChE and ChAT accompanied by a similar decrement of MnSOD, but not of Cu/ZnSOD provided neurochemical substrates for the behavioral changes. Each of the single drug administrations protected against the neurotoxic events, whereas the combined treatment failed to ameliorate beta A toxicity.
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PMID:N-Methyl-D-aspartate receptor antagonist MK-801 and radical scavengers protect cholinergic nucleus basalis neurons against beta-amyloid neurotoxicity. 1034 26

The involvement of NMDA and AMPA/kainate receptors in the induction of superoxide radical production in the rat brain was examined after injection of kainate, non-NMDA receptor agonist, kainate plus 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), selective AMPA/kainate receptor antagonist, or kainate plus 2-amino-5-phosphonopentanoic acid (APV), selective NMDA receptor antagonist. Competitive glutamate receptor antagonists were injected with kainate unilaterally into the CA3 region of the rat hippocampus. We investigated superoxide production and mitochondrial MnSOD activity after injection. The measurements took place at different times (5, 15 min, 2, 48 h and 7 days) in the ipsi- and contralateral hippocampus, forebrain cortex, striatum, and cerebellum homogenates. Used glutamate antagonists APV and CNQX both expressed sufficient neuroprotection in sense of decreasing superoxide production and increasing MnSOD levels, but with differential effect in mechanisms and time dynamics. Our findings suggest that NMDA and AMPA/kainate receptors are differentially involved in superoxide production. Following intrahippocampal antagonists injection they, also, interpose different neuroprotection effect on the induction of MnSOD activity in distinct brain regions affected by the injury, which are functionally connected via afferents and efferents. It suggests that MnSOD protects the cells in these regions from superoxide-induced damage and therefore may limit the retrograde and anterograde spread of neurotoxicity.
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PMID:Differential effects of NMDA and AMPA/kainate receptor antagonists on superoxide production and MnSOD activity in rat brain following intrahippocampal injection. 1527 61