title: The Guanine-Based Purinergic System: The Tale of An Orphan Neuromodulation.
abstract: Guanine-based purines (GBPs) have been recently proposed to be not only metabolic agents but also extracellular signaling molecules that regulate important functions in the central nervous system. In such way, GBPs-mediated neuroprotection, behavioral responses and neuronal plasticity have been broadly described in the literature. However, while a number of these functions (i.e., GBPs neurothophic effects) have been well-established, the molecular mechanisms behind these GBPs-dependent effects are still unknown. Furthermore, no plasma membrane receptors for GBPs have been described so far, thus GBPs are still considered orphan neuromodulators. Interestingly, an intricate and controversial functional interplay between GBPs effects and adenosine receptors activity has been recently described, thus triggering the hypothesis that GBPs mechanism of action might somehow involve adenosine receptors. Here, we review recent data describing the GBPs role in the brain. We focus on the involvement of GBPs regulating neuronal plasticity, and on the new hypothesis based on putative GBPs receptors. Overall, we expect to shed some light on the GBPs world since although these molecules might represent excellent candidates for certain neurological diseases management, the lack of putative GBPs receptors precludes any high throughput screening intent for the search of effective GBPs-based drugs.
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo Palermo, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Di Liberto
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo Palermo, Italy.
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Mudò
authors.affiliation: Department of Biomedical and Biotechnological Sciences, Unit of Medical Biochemistry, University of Catania Catania, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Garozzo
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo Palermo, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Frinchi
authors.affiliation: Department of Pathology and Experimental Therapeutics, Faculty of Medicine, Bellvitge Biomedical Research Institute, Institute of Neurosciences, University of Barcelona Barcelona, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Fernandez-Dueñas
authors.affiliation: Department of Medical, Oral and Biotecnological Sciences, University of Chieti-Pescara Chieti, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Di Iorio
authors.affiliation: Department of Medical, Oral and Biotecnological Sciences, University of Chieti-Pescara Chieti, Italy.
authors.forename: Renata
authors.initials: R
authors.lastname: Ciccarelli
authors.affiliation: Department of Medical, Oral and Biotecnological Sciences, University of Chieti-Pescara Chieti, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Caciagli
authors.affiliation: Department of Biomedical and Biotechnological Sciences, Unit of Medical Biochemistry, University of Catania Catania, Italy.
authors.forename: Daniele F
authors.initials: DF
authors.lastname: Condorelli
authors.affiliation: Department of Pathology and Experimental Therapeutics, Faculty of Medicine, Bellvitge Biomedical Research Institute, Institute of Neurosciences, University of Barcelona Barcelona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Ciruela
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo Palermo, Italy.
authors.forename: Natale
authors.initials: N
authors.lastname: Belluardo
keywords: adenosine; guanine-based purines; guanosine; neuroprotection; purinergic receptors; synaptic plasticity