Limits...
Guanosine: a Neuromodulator with Therapeutic Potential in Brain Disorders

View Article: PubMed Central - PubMed

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 of in vivo and in vitro studies 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.

No MeSH data available.


Related in: MedlinePlus

Schematic illustration of the neurotrophic effects of guanosine. In astrocytes cerebellar cultures guanosine promotes the reorganization of extracellular matrix proteins fibronectin and laminin (photomicrographs from Decker H. and colleagues [145]) via CaMKII, PKA, MAPK/ERK, PKC and PI3K/AKT activation (1) [145]. Guanosine also increases the number of cerebellar neurons in culture (or in coculture with astrocytes) by activation of these kinases. This guanosine neurotrophic effect involves A2AR activation and it is also dependent on NMDAR and Kainate receptors activation (2) [39]. In neural stem cells guanosine increases intracellular cAMP, CREB phosphorylation and BDNF mRNA levels (3) [62]. Guanosine promotes neurite outgrowth in cerebellar neurons culture by PKC activation (4) [143] and in PC12 by heme-oxygenase (HO-1) induction (5) [144]. In cultured astrocytes, guanosine promotes cellular proliferation (6) [116] and synthesis and release of neurotrophic factors, as FGF-2 and NGF (7) [141]. These neurotrophic effects of guanosine may be involved in cell survival. Figure designed using images from www.servier.com/Powerpoint-image-bank.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5036959&req=5

F3-ad-7-5-657: Schematic illustration of the neurotrophic effects of guanosine. In astrocytes cerebellar cultures guanosine promotes the reorganization of extracellular matrix proteins fibronectin and laminin (photomicrographs from Decker H. and colleagues [145]) via CaMKII, PKA, MAPK/ERK, PKC and PI3K/AKT activation (1) [145]. Guanosine also increases the number of cerebellar neurons in culture (or in coculture with astrocytes) by activation of these kinases. This guanosine neurotrophic effect involves A2AR activation and it is also dependent on NMDAR and Kainate receptors activation (2) [39]. In neural stem cells guanosine increases intracellular cAMP, CREB phosphorylation and BDNF mRNA levels (3) [62]. Guanosine promotes neurite outgrowth in cerebellar neurons culture by PKC activation (4) [143] and in PC12 by heme-oxygenase (HO-1) induction (5) [144]. In cultured astrocytes, guanosine promotes cellular proliferation (6) [116] and synthesis and release of neurotrophic factors, as FGF-2 and NGF (7) [141]. These neurotrophic effects of guanosine may be involved in cell survival. Figure designed using images from www.servier.com/Powerpoint-image-bank.

Mentions: In the CNS, extracellular guanosine stimulates trophic effects on astrocytes and neurons [116, 138, 139]. Guanosine neurotrophic effects are depicted in Fig. 3.


Guanosine: a Neuromodulator with Therapeutic Potential in Brain Disorders
Schematic illustration of the neurotrophic effects of guanosine. In astrocytes cerebellar cultures guanosine promotes the reorganization of extracellular matrix proteins fibronectin and laminin (photomicrographs from Decker H. and colleagues [145]) via CaMKII, PKA, MAPK/ERK, PKC and PI3K/AKT activation (1) [145]. Guanosine also increases the number of cerebellar neurons in culture (or in coculture with astrocytes) by activation of these kinases. This guanosine neurotrophic effect involves A2AR activation and it is also dependent on NMDAR and Kainate receptors activation (2) [39]. In neural stem cells guanosine increases intracellular cAMP, CREB phosphorylation and BDNF mRNA levels (3) [62]. Guanosine promotes neurite outgrowth in cerebellar neurons culture by PKC activation (4) [143] and in PC12 by heme-oxygenase (HO-1) induction (5) [144]. In cultured astrocytes, guanosine promotes cellular proliferation (6) [116] and synthesis and release of neurotrophic factors, as FGF-2 and NGF (7) [141]. These neurotrophic effects of guanosine may be involved in cell survival. Figure designed using images from www.servier.com/Powerpoint-image-bank.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5036959&req=5

F3-ad-7-5-657: Schematic illustration of the neurotrophic effects of guanosine. In astrocytes cerebellar cultures guanosine promotes the reorganization of extracellular matrix proteins fibronectin and laminin (photomicrographs from Decker H. and colleagues [145]) via CaMKII, PKA, MAPK/ERK, PKC and PI3K/AKT activation (1) [145]. Guanosine also increases the number of cerebellar neurons in culture (or in coculture with astrocytes) by activation of these kinases. This guanosine neurotrophic effect involves A2AR activation and it is also dependent on NMDAR and Kainate receptors activation (2) [39]. In neural stem cells guanosine increases intracellular cAMP, CREB phosphorylation and BDNF mRNA levels (3) [62]. Guanosine promotes neurite outgrowth in cerebellar neurons culture by PKC activation (4) [143] and in PC12 by heme-oxygenase (HO-1) induction (5) [144]. In cultured astrocytes, guanosine promotes cellular proliferation (6) [116] and synthesis and release of neurotrophic factors, as FGF-2 and NGF (7) [141]. These neurotrophic effects of guanosine may be involved in cell survival. Figure designed using images from www.servier.com/Powerpoint-image-bank.
Mentions: In the CNS, extracellular guanosine stimulates trophic effects on astrocytes and neurons [116, 138, 139]. Guanosine neurotrophic effects are depicted in Fig. 3.

View Article: PubMed Central - PubMed

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 of in vivo and in vitro studies 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.

No MeSH data available.


Related in: MedlinePlus