Guanosine and its role in neuropathologies

Abstract

Guanosine is a purine nucleoside thought to have neuroprotective properties. It is released in the brain under physiological conditions and even more during pathological events, reducing neuroinflammation, oxidative stress, and excitotoxicity, as well as exerting trophic effects in neuronal and glial cells. In agreement, guanosine was shown to be protective in several in vitro and/or in vivo experimental models of central nervous system (CNS) diseases including ischemic stroke, Alzheimer's disease, Parkinson's disease, spinal cord injury, nociception, and depression. The mechanisms underlying the neurobiological properties of guanosine seem to involve the activation of several intracellular signaling pathways and a close interaction with the adenosinergic system, with a consequent stimulation of neuroprotective and regenerative processes in the CNS. Within this context, the present review will provide an overview of the current literature on the effects of guanosine in the CNS. The elucidation of the complex signaling events underlying the biochemical and cellular effects of this nucleoside may further establish guanosine as a potential therapeutic target for the treatment of several neuropathologies.

Anti-aging effects of guanosine in glial cells

“…Guanosine has been studied in a variety of experimental models, including seizures, hypoxia, glucose deprivation, oxidative injury, and inflammatory conditions [4,5,[37][38][39][40]. Because guanosine may be released from glial cells, modulating important glial functions, astrocytes emerge as central players in the protective actions of guanosine [12,14].…”

“…Guanine-based purines are known to act as extracellular signaling molecules, exerting trophic and neuroprotective roles in in vitro and in vivo experimental models [1][2][3][4][5]. Guanosine, more specifically, has been shown to induce numerous beneficial cellular responses in several brain injuries, such as seizures, hypoxia, anxiety-like behavior, ischemia, and glucose deprivation [1,[6][7][8][9].…”

Cell wall‐anchored 5′‐nucleotidases in Gram‐positive cocci

“…Mammalian CD73 can use GMP as an alternative purine 5′‐monophosphate, but prefers AMP, whereas pyrimidines are not hydrolyzed (Heuts et al, ). Extracellular guanosine is a known signaling molecule in the brain with neuroprotective properties (Bettio, Gil‐Mohapel, & Rodrigues, ), but seems to lack a function in immune signaling. While the addition of exogenous Ado to a S. aureus adsA deletion mutant specifically increased survival of the mutant in whole blood, addition of guanosine showed no effect (Thammavongsa et al, ).…”

Oocyte Meiotic Resumption under High Surveillance

“…Thus, the inhibitory effect of the combination of both ADO and GUO are somewhat additive according to the concentration used. Although GUO is proposed to activate a specific G-protein-coupled receptor with the involvement of P1 receptor [29], it has been recently reported that GUO functions as an extracellular signaling molecule without the need for GUO receptors [30]. In vascular smooth muscle cells, extracellular GUO regulated extracellular ADO [30].…”