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The Adenosinergic System pp 101–126Cite as

Purines in Parkinson’s: Adenosine A2A Receptors and Urate as Targets for Neuroprotection

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Part of the book series: Current Topics in Neurotoxicity ((Current Topics Neurotoxicity,volume 10))

Abstract

Purines are essential constituents of all living cells. The nucleoside adenosine is not only a precursor of ATP and cyclic AMP but is also released by a wide variety of cells under various physiological and pathological conditions. In mammals, adenosine acts on four subtypes of guanine nucleotide binding protein (G protein)-coupled receptor (GPCR)—A1, A2A, A2B and A3. Among these the adenosine A2A receptor has emerged as a particularly attractive target of therapeutics development for Parkinson’s disease (PD), in part because it is highly expressed in brain regions innervated by the dopaminergic neurons that degenerate in PD. Urate (also known as uric acid —2,6,8-trioxypurine) is the most abundant plasma antioxidant as well as the end product of purine metabolism in humans. Emerging clinical, epidemiological, and laboratory evidence has identified urate as a potential neuroprotectant for the treatment of PD. The primary intent of this review is to explore the neuroprotective effects of adenosine receptor antagonists and urate and their therapeutic potential in PD with particular attention to epidemiological and preclinical findings linking these purines to PD and other neurodegenerative diseases. This review also summarizes current clinical development of purines as candidate neuroprotectants.

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Acknowledgements

The authors would like to thank the Dept of Defense/NETPR program W81XWH-11-1-0150 and NIH R21NS084710 for the funding. The authors declare no competing financial interests.

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  1. Molecular Neurobiology Laboratory, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, 114, 16th street, Rm 3001, 02129, Boston, MA, USA

    Rachit Bakshi PhD

  2. Molecular Neurobiology Laboratory, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 02129, Boston, MA, USA

    Robert Logan & Michael A. Schwarzschild

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Correspondence to Rachit Bakshi PhD .

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  1. Dept. of Biomedical Sciences Section of Neuropsychopharmacology, University of Cagliari, Cagliari, Italy

    Micaela Morelli

  2. Dept. of Biomedical Sciences Section of Neuropsychopharmacology, University of Cagliari, Cagliari, Italy

    Nicola Simola

  3. Dept. of Neuropsychopharmacology Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

    Jadwiga Wardas

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Bakshi, R., Logan, R., Schwarzschild, M. (2015). Purines in Parkinson’s: Adenosine A2A Receptors and Urate as Targets for Neuroprotection. In: Morelli, M., Simola, N., Wardas, J. (eds) The Adenosinergic System. Current Topics in Neurotoxicity, vol 10. Springer, Cham. https://doi.org/10.1007/978-3-319-20273-0_6

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