LAUSR

Over the years, increasing data concerning the extracellular effect of guanine-based purines have been published. This class of molecules that embraces the well-known nucleotides GTP, GDP and GMP, the nucleoside guanosine (GUO) and the nucleobase guanine are necessary for the maintenance of important intracellular processes, such as nucleic acid structure, energetic metabolism, and signal transduction via G-proteins (Hepler and Gilman 1992). Besides that, guanine-based purines extracellular effects are also noteworthy, mainly through its nucleoside GUO. In the central nervous system (CNS), GUO acts as a neuromodulator mediating several cellular processes, including cell growth, differentiation and survival (Lanznaster, et al., 2016; Schmidt, Lara, and Souza 2007). Also, GUO exerts protective effects in several models of neurotoxicity or neurological disorders (both in vitro and in vivo). GUO presents anxiolytic (Bettio et al., 2014), antidepressant-like (Bettio et al., 2012), antinociceptive (Schmidt et al., 2010), and anticonvulsant effects (Lara et al., 2001) in rodents. GUO treatment exerts neuroprotection on Alzheimer’s and Parkinson’s disease in vivo models, ameliorating behavior, cognitive and motor function (Su et al., 2009; Massari et al., 2017; Lanznaster, et al., 2016; Marques et al., 2019; da Silva et al., 2020). In vitro studies showed that GUO modulates glutamate uptake, decreases the production of reactive oxygen species (ROS), improves mitochondrial function and presents anti-inflammatory properties (DalCim et al., 2012; Marques, et al., 2019; Frizzo et al., 2003; Dal-Cim et al., 2019). Regarding trophic effects, GUO increases the number of neurons in culture (Decker et al., 2019) and recently it was shown that GUO promotes neural stem cell proliferation and neuronal differentiation in vitro. Additionally, GUO in vivo treatment increases the number of dividing cells and also increases neurogenesis in the hippocampal dentate gyrus (Piermartiri et al., 2020).