کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6264086 | 1613950 | 2012 | 7 صفحه PDF | دانلود رایگان |
Development and progression of neurodegenerative disorders have, amongst other potential causes, been attributed to a disruption of iron regulatory mechanisms and iron accumulation. Excess extracellular iron may enter cells via nontraditional routes such as voltage-gated calcium channels and N-methyl-d-aspartate (NMDA) receptors leading to intracellular oxidative damage and ultimately mitochondrial failure. Nimodipine, an L-type calcium channel blocker has been shown to reduce iron-induced toxicity in neuronal and brain endothelial cells. Our current study investigates NGP1-01, a multimodal drug acting as an antagonist at both the NMDA receptor and the L-type calcium channel. Our previous studies support NGP1-01 as a promising neuroprotective agent in diseases involving calcium-related excitotoxicity. We demonstrate here that NGP1-01 (1 and 10 μM) pretreatment abrogates the effects of iron overload in brain endothelial cells protecting cellular viability. Both concentrations of NGP1-01 were found to attenuate iron-induced reduction in cellular viability to a similar extent, and were statistically significant. To further verify the mechanism, the L-type calcium channel agonist FPL 64176 was administered to promote iron uptake. Addition of NGP1-01 dose-dependently reduced FPL 64176 stimulated uptake of iron. These data support further evaluation of NGP1-01 as a neuroprotective agent, not only in diseases associated with excitotoxicity, but also in those of iron overload.
⺠NGP1-01, a polycyclic cage amine, demonstrates neuro-protective properties in iron overload. ⺠NGP1-01 reduces iron accumulation in rat brain endothelial cells. ⺠NGP1-01 attenuates iron-induced apoptosis. ⺠NGP1-01 is a promising neuro-protective candidate for Alzheimer's and Parkinson's patients.
Journal: Brain Research - Volume 1489, 13 December 2012, Pages 133-139