title: Guanosine: a Neuromodulator with Therapeutic Potential in Brain Disorders.
abstract: Guanosine is a purine nucleoside with important functions in cell metabolism and a protective role in response to degenerative diseases or injury. The past decade has seen major advances in identifying the modulatory role of extracellular action of guanosine in the central nervous system (CNS). Evidence from rodent and cell models show a number of neurotrophic and neuroprotective effects of guanosine preventing deleterious consequences of seizures, spinal cord injury, pain, mood disorders and aging-related diseases, such as ischemia, Parkinson's and Alzheimer's diseases. The present review describes the findings ofin vivoandin vitrostudies and offers an update of guanosine effects in the CNS. We address the protein targets for guanosine action and its interaction with glutamatergic and adenosinergic systems and with calcium-activated potassium channels. We also discuss the intracellular mechanisms modulated by guanosine preventing oxidative damage, mitochondrial dysfunction, inflammatory burden and modulation of glutamate transport. New and exciting avenues for future investigation into the protective effects of guanosine include characterization of a selective guanosine receptor. A better understanding of the neuromodulatory action of guanosine will allow the development of therapeutic approach to brain diseases.
authors.affiliation: 2Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina-UFSC, Campus Trindade, 88040-900, Florianópolis, SC, Brazil; 3CAPES Foundation, Ministry of Education of Brazil, Brasília - DF 70040-020, Brazil.
authors.forename: Débora
authors.initials: D
authors.lastname: Lanznaster
authors.affiliation: 2Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina-UFSC, Campus Trindade, 88040-900, Florianópolis, SC, Brazil; 3CAPES Foundation, Ministry of Education of Brazil, Brasília - DF 70040-020, Brazil.
authors.forename: Tharine
authors.initials: T
authors.lastname: Dal-Cim
authors.affiliation: 2Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina-UFSC, Campus Trindade, 88040-900, Florianópolis, SC, Brazil; 3CAPES Foundation, Ministry of Education of Brazil, Brasília - DF 70040-020, Brazil.
authors.forename: Tetsadê C B
authors.initials: TC
authors.lastname: Piermartiri
authors.affiliation: 1Departamento de Bioquímica,; 2Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina-UFSC, Campus Trindade, 88040-900, Florianópolis, SC, Brazil.
authors.forename: Carla I
authors.initials: CI
authors.lastname: Tasca
keywords: adenosine; glutamate; guanosine; neuromodulator; neuroprotection; neurotrophic effects; purines