Nucleotides have shown to be effective in the treatment of diverse neurological peripheral syndromes and nucleotide containing drugs, such as Nucleo CMP Forte ® have been prescribed to patients with lumbosciatalgia, alcoholic and diabetic polyneuropathies or trigeminal neuralgia, although their mechanism of action remains to be established. Nucleo CMP Forte ® is a commercial nucleotide-based drug, consisting of uridinemonophosphate (UMP), uridinediphosphate (UDP), uridinetriphosphate (UTP) and cytidinemonophosphate (CMP). MPP + treated cells show signs of apoptosis and the toxin appears to act at oxidative-stress level, with the induction of p53, opening of the mitochondrial membrane transition pore and activation of the JNK pathway, although the specific mechanisms are not fully understood. On the other hand, treatment of neuronal cultured cells with 1-methyl 4- phenyl 1, 2, 3, 6-tetrahydropyridine (MPTP) is currently studied as a model of Parkinson’s disease. Zhang and Bhavnani report that changes that occur in apoptosis depend on the neuron cell type. The neuronal death induced by glutamate is mediated by activation of the N-methyl-D-aspartate (NMDA)-subtype receptor of Glu and involves an increase in intracellular calcium concentrations that leads to an intracellular cascade of cytotoxic events.

This phenomenon, named excitotoxicity, has also been implicated in epileptic seizures and various chronic and progressive neurodegenerative diseases, such as Huntington’s chorea, Alzheimer’s disease, and Parkinson’s disease. Injury (trauma or ischemia) in the brain triggers an abnormal release of glutamate and other excitatory aminoacids that contribute significantly to neuronal death. 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. More interestingly, drug pre-treatment significantly reduced MPP +- and glutamate-induced cell death in SH-SY5Y cells and in rat cortical cells. 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. Cell viability was measured at different times. 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. 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. Its effects on brain pathologies has received little attention. It has been prescribed for peripheral nervous system disorders, such as lumbosciatalgia, diabetic or alcoholic polyneuropathy, or trigeminal neuralgia. Nucleo CMP Forte ® is a nucleotide-based drug consisting of cytidinemonophosphate, uridinemonophosphate, uridinediphosphate and uridinetriphosphate. Keywords: Cortical Cell Culture, Nucleotides, Excitotoxicity, Glutamate Neuroprotection, Parkinson’s Disease, SH-SY5Y Cells 1Basic Sciences Department, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Barcelona, Spain 2Neuroscience Institute, Universitat Autònoma de Barcelona, Barcelona, Spain 3Centro de Investigación Biomédica en Red de la Fisiopatologia de la Obesidad y Nutrición (CIBER-OBN), Barcelona, Spain.Įmail: February 22 nd, 2011 revised April 23 rd, 2011 accepted May 10 th, 2011.

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