Lessons from the physiological role of guanosine in neurodegeneration and cancer: Toward a multimodal mechanism of action?

Autor: Tasca CI; Department of Biochemistry, Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, SC, Brazil. carla.tasca@ufsc.br.; Laboratory of Neurochemistry-4, Neuroscience Program/Biochemistry Program, Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, SC, Brazil. carla.tasca@ufsc.br., Zuccarini M; Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, 66100, Chieti, Italy.; Center for Advanced Studies and Technologies (CAST), University of Chieti-Pescara, 66100, Chieti, Italy., Di Iorio P; Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, 66100, Chieti, Italy.; Center for Advanced Studies and Technologies (CAST), University of Chieti-Pescara, 66100, Chieti, Italy., Ciruela F; Pharmacology Unit, Department of Pathology and Experimental Therapeutics, School of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.; Neuropharmacology & Pain Group, Neuroscience Program, Bellvitge Institute for Biomedical Research, 08907L'Hospitalet de Llobregat, Bellvitge, Spain.
Jazyk: angličtina
Zdroj: Purinergic signalling [Purinergic Signal] 2024 Jul 15. Date of Electronic Publication: 2024 Jul 15.
DOI: 10.1007/s11302-024-10033-y
Abstrakt: Neurodegenerative diseases and brain tumours represent important health challenges due to their severe nature and debilitating consequences that require substantial medical care. Interestingly, these conditions share common physiological characteristics, namely increased glutamate, and adenosine transmission, which are often associated with cellular dysregulation and damage. Guanosine, an endogenous nucleoside, is safe and exerts neuroprotective effects in preclinical models of excitotoxicity, along with cytotoxic effects on tumour cells. However, the lack of well-defined mechanisms of action for guanosine hinders a comprehensive understanding of its physiological effects. In fact, the absence of specific receptors for guanosine impedes the development of structure-activity research programs to develop guanosine derivatives for therapeutic purposes. Alternatively, given its apparent interaction with the adenosinergic system, it is plausible that guanosine exerts its neuroprotective and anti-tumorigenic effects by modulating adenosine transmission through undisclosed mechanisms involving adenosine receptors, transporters, and purinergic metabolism. Here, several potential molecular mechanisms behind the protective actions of guanosine will be discussed. First, we explore its potential interaction with adenosine receptors (A 1 R and A 2A R), including the A 1 R-A 2A R heteromer. In addition, we consider the impact of guanosine on extracellular adenosine levels and the role of guanine-based purine-converting enzymes. Collectively, the diverse cellular functions of guanosine as neuroprotective and antiproliferative agent suggest a multimodal and complementary mechanism of action.
(© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
Databáze: MEDLINE
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