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

Abstract

Nucleo CMP Forte<sup>®</sup> 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<sup>+</sup>), 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<sup>+</sup> or glutamate at a range of concentrations. Cell viability was measured at different times. Nucleo CMP Forte<sup>®</sup> 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<sup>+</sup>- 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<sup>®</sup> are promising therapeutic molecules for the prevention of neuronal death in brain caused by focal ischemia, Parkinson’s disease or other neurodegenerative pathologies

Pyrimidine Nucleoside-Mediate Prevention of Neurobehavioral Consequences Related to Cerebral Ischemia in Rat Models

“…Both nucleosides play an important role during the regulation of brain functions [2], since it has been described that concentration of these compounds are decreased under ischemic conditions [3,4]. Cytidine monophosphate (CMP) mediates the synthesis of the complex lipids that form part of the neuronal membrane, particularly sphingomyelin, which is the parent substance of the myelin sheath as well as a precursor of DNA and RNA nucleic acids [1,[5][6][7]. On the other hand, uridine (as a precursor metabolite) supports the synthesis of different molecules involved in diverse neural processes.…”