Purinergic signaling in Parkinson's disease. Relevance for treatment

• Published in: Neuropharmacology 2016-05, Vol.104, p.161-168
• Main Authors: Navarro, Gemma, Borroto-Escuela, Dasiel O., Fuxe, Kjell, Franco, Rafael
• Format: Article
• Language: English
• Subjects: Adenosine - metabolism; Adenosine A2 Receptor Antagonists - metabolism; Adenosine receptor antagonist; Adenosine receptors; Animals; ATP receptors; Basal Ganglia - metabolism; Corpus Striatum - metabolism; GPCR heteromer; Humans; Parkinson Disease - drug therapy; Parkinson Disease - metabolism; Parkinson's disease; Purine Nucleotides - metabolism; Purines - therapeutic use; Pyrimidines - therapeutic use; Receptor, Adenosine A2A - metabolism; Receptors, Dopamine D2 - metabolism; Signal Transduction; Triazoles - therapeutic use
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2015.07.024

Purinergic signaling modulates dopaminergic neurotransmission in health and disease. Classically adenosine A1 and A2A receptors have been considered key for the fine tune control of dopamine actions in the striatum, the main CNS motor control center. The main adenosine signaling mechanism is via the cAMP pathway but the future will tell whether calcium signaling is relevant in adenosinergic control of striatal function. Very relevant is the recent approval in Japan of the adenosine A2A receptor antagonist, istradefylline, for use in Parkinson's disease patients. Purine nucleotides are also regulators of striatal dopamine neurotransmission via P2 purinergic receptors. In parallel to the alpha-synuclein hypothesis of Parkinson's disease etiology, purinergic P2X1 receptors have been identified as mediators of accumulation of the Lewy-body enriched protein alpha-synuclein. Of note is the expression in striatum of purinergic-receptor-containing heteromers that are potential targets of anti-Parkinson's disease therapies and should be taken into account in drug discovery programs. This article is part of the Special Issue entitled ‘Purines in Neurodegeneration and Neuroregeneration’. •Adenine nucleotides and adenosine are important regulators of dopaminergic transmission in striatum.•Purinergic signalling in striatum is mediated by P1 (adenosine) and P2 (purine nucleotide) receptors.•Adenosine A2A receptor antagonists, such as istradefylline, have potential in the therapy of Parkinson's disease.•Istradefylline is a first in class molecule approved in Japan for use in parkinsonian patients.