A Nucleotide-Based Drug Protects against Glutamate- and MPP-Induced Neurotoxicity

Nucleo CMP Forte is a nucleotide-based drug consisting of cytidinemonophosphate, uridinemonophosphate, uridinediphosphate and uridinetriphosphate. It has been prescribed for peripheral nervous system disorders, such as lumbosciatalgia, diabetic or alcoholic polyneuropathy, or trigeminal neuralgia. Its effects on brain pathologies has received little attention. We examined its neuroprotective effects on cell toxicity induced by glutamate excitotoxicity or by 1methyl-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 MPPand 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.