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Guanosine and its role in neuropathologies

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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.

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Abbreviations

6-OHDA:

6-Hydroxydopamine

ARS:

Acute restraint stress

ATP:

Adenosine 5′-triphosphate

Aβ:

Amyloid β-peptide

CNS:

Central nervous system

cAMP:

Cyclic adenosine monophosphate

CREB:

cAMP response element binding protein

FGF-2:

Fibroblast growth factor 2

FST:

Forced swimming test

GBP:

Guanine-based purine

GDP:

Guanosine 5′-diphosphate

GMP:

Guanosine 5′-monophosphate

GTP:

Guanosine 5′-triphosphate 1-methyl-4-phenylpyridinium

iNOS:

Inducible nitric oxide synthase

MAPK:

Mitogen-activated protein kinase

NMDAR:

N-methyl-D-aspartate receptor

NGF:

Nerve growth factor

NF-κB:

Nuclear factor-kappaB

OGD:

Oxygen and glucose deprivation

PC12:

Pheochromocytoma

PI3K:

Phosphatidylinositol-3 kinase

QA:

Quinolinic acid

ROS:

Reactive oxygen species

SCI:

Spinal cord injury

SOD:

Superoxide dismutase

TST:

Tail suspension test

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Acknowledgments

L.B., J.G.M., and A.L.S.R. acknowledge funding from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Project #403120/2012-8 of the Brazilian Federal Government. A.L.S.R. is a CNPq Research Fellow.

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  1. Department of Biochemistry, Center of Biological Sciences, Federal University of Santa Catarina, 88040-900, Florianópolis, SC, Brazil

    Luis E. B. Bettio & Ana Lúcia S. Rodrigues

  2. Division of Medical Sciences and UBC Island Medical Program, University of Victoria, Victoria, BC, V8W 2Y2, Canada

    Luis E. B. Bettio & Joana Gil-Mohapel

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Bettio, L.E.B., Gil-Mohapel, J. & Rodrigues, A.L.S. Guanosine and its role in neuropathologies. Purinergic Signalling 12, 411–426 (2016). https://doi.org/10.1007/s11302-016-9509-4

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