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A Nucleotide-based Drug Protects Against Glutamate-and MPP^(+)-Induced Neurotoxicity

Neuroscience & Medicine 2011年第2期2卷 154-160页

作者： Alejandro Gella Tania Martianez Aloa Lamarca Cristina Gutierrez nuria Durany nuria casals Basic Sciences Department Faculty of Medicine and Health SciencesUniversitat Internacional de CatalunyaBarcelonaSpain Neuroscience Institute Universitat Autònoma de BarcelonaBarcelonaSpain Centro de Investigación Biomédica en Red de la Fisiopatologia de la Obesidad y Nutrición(CIBER-OBN) BarcelonaSpain

Nucleo CMP Forte? is a nucleotide-based drug consisting of cytidinemonophosphate, uridinemonophosphate, uridin-ediphosphate and uridinetriphosphate. It has been prescribed for peripheral nervous system disorders, such as lum-bosciatalgia, diabetic or alcoholic polyneuropathy, or trigeminal neuralgia. Its effects on brain pathologies has re-ceived little attention. We examined its neuroprotective effects on cell toxicity induced by glutamate excitotoxicity or by 1-methyl-4-phenyl-pyridinium (MPP+), an in vitro cell model of Parkinson’s disease. We used the human dopaminergic cell line SH-SY5Y and a primary culture of rat cortical cells pre-treated with the drug for 24 hours and then exposed to MPP+ or glutamate at a range of concentrations. Cell viability was measured at different times. Nucleo CMP Forte? pre-treatment significantly increased the rate of cell division in SH-SY5Y cells, as well as the synthesis of triglycerides and phospholipids. More interestingly, drug pre-treatment significantly reduced MPP+- and glutamate-induced cell death in SH-SY5Y cells and in rat cortical cells. These results indicate that the nucleotides included in Nucleo CMP Forte? are promising therapeutic molecules for the prevention of neuronal death in brain caused by focal ischemia, Parkinson’s disease or other neurodegenerative pathologies.

关键词： Cortical Cell Culture Nucleotides Excitotoxicity Glutamate Neuroprotection Parkinson’s Disease SH-SY5Y Cells

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