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Panminerva Medica 2012 December;54(1 Suppl 4):43-51

Copyright © 2012 EDIZIONI MINERVA MEDICA

lingua: Inglese

Protective activity of guanosine in an in vitro model of Parkinson’s disease

Giuliani P. 1, Romano S. 1, Ballerini P. 2, Ciccarelli R. 1, Petragnani N. 1, Cicchitti S. 1, Zuccarini M. 1, Jiang S. 3, Rathbone MP. 4, Caciagli F. 1, Di Iorio P. 1

1 Department of Experimental and Clinical Sciences University of Chieti-Pescara, Chieti, Italy; 2 Department of Psychologic, Humanities and Territoral Sciences, University of Chieti-Pescara, Chieti, Italy; 3 Department of Surgery, McMaster University, Canada; 4 Department of Medicine, McMaster University, Canada


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Parkinson’s disease (PD) is a pathological condition characterized by a progressive neurodegeneration of dopaminergic neurons with the consequent reduction of dopamine content in the substantia nigra. The neurotoxin 6-hydroxydopamine (6-OHDA) is widely used to mimic the neuropathology of PD in both in vivo and in vitro experimental models. We found that, as expected, in dopaminergic human SH-SY5Y neuroblastoma cells the toxin reduced cell viability causing programmed cell death as assessed by an increase in DNA fragmentation. We also examined, in these cells, the activation/inactivation of several pro and anti apoptotic signaling pathways by 6-OHDA including p-38 kinase (p-38), c-Jun N-terminal kinase (JNK), protein kinase B (also known as Akt), glycogen synthase kinase-3β (GSK3β), and Bcl-2 protein. Guanine-based purines, exert neuroprotective effects and we previously reported that guanosine activates cell survival pathways including PI3K/Akt/PKB signaling in different kinds of cells including glia and neuroblastoma cells. In the present study we found that guanosine (300 µM) protected SH-SY5Y neuroblastoma cells when they were exposed to 6-OHDA, promoting their survival. Guanosine reduced the 6-OHDA mediated activation of p-38 and JNK. Moreover the nucleoside potentiated the early increase in the phosphorylation of the anti-apoptotic kinase Akt and the increase in the expression of the anti-apoptotic Bcl-2 protein induced by 6-OHDA. In summary our results show that guanosine results to be neuroprotective in a recognized in vitro model of PD thus suggesting that it could represent a new potential pharmacological tool to be studied in the therapeutic approach to PD.

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