Pathophysiological roles for purines: adenosine, caffeine and urate.
The motor symptoms of Parkinson's disease (PD) are primarily due to the degeneration of the dopaminergic neurons in the nigrostriatal pathway. However, several other brain areas and neurotransmitters other than dopamine such as noradrenaline, 5-hydroxytryptamine and acetylcholine are affected in the disease. Moreover, adenosine because of the extensive interaction of its receptors with the dopaminergic system has been implicated in the pathophysiology of the disease. Based on the involvement of these non-dopaminergic neurotransmitters in PD and the sometimes severe adverse effects that limit the mainstay use of dopamine-based anti-parkinsonian treatments, recent assessments have called for a broadening of therapeutic options beyond the traditional dopaminergic drug arsenal. In this review we describe the interactions between dopamine and adenosine receptors that underpin the pre-clinical and clinical rationale for pursuing adenosine A(2A) receptor antagonists as symptomatic and potentially neuroprotective treatment of PD. The review will pay particular attention to recent results regarding specific A(2A) receptor-receptor interactions and recent findings identifying urate, the end product of purine metabolism, as a novel prognostic biomarker and candidate neuroprotectant in PD.
Morelli
Micaela
M
Department of Toxicology, University of Cagliari, Cagliari, Italy. morelli@unica.it
Carta
Anna R
AR
Kachroo
Anil
A
Schwarzschild
Michael A
MA
D000241:Adenosine / Q000378:metabolism*; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D002110:Caffeine / Q000378:metabolism / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000453:epidemiology / Q000503:physiopathology* / Q000517:prevention & control; D011687:Purines / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D014527:Uric Acid / Q000378:metabolism
D058917:Adenosine A2 Receptor Antagonists; D018696:Neuroprotective Agents; D011687:Purines; D043705:Receptor, Adenosine A2A; D014527:Uric Acid; D002110:Caffeine; D000241:Adenosine; D004298:Dopamine