title: Purinergic signaling in Parkinson's disease. Relevance for treatment.
abstract: 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'.
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain; Centro de Investigación en Red, Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: dimartts@hotmail.com.
authors.forename: Gemma
authors.initials: G
authors.lastname: Navarro
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Earth, Life and Environmental Sciences, Section of Physiology, Campus Scientifico Enrico Mattei, University of Urbino, Urbino, Italy. Electronic address: Dasiel.Borroto-Escuela@ki.se.
authors.forename: Dasiel O
authors.initials: DO
authors.lastname: Borroto-Escuela
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. Electronic address: Kjell.Fuxe@ki.se.
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain; Centro de Investigación en Red, Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: rfranco@ub.edu.
authors.forename: Rafael
authors.initials: R
authors.lastname: Franco
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D058917:Adenosine A2 Receptor Antagonists / Q000378:metabolism; D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D006801:Humans; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism*; D011685:Purine Nucleotides / Q000378:metabolism; D011687:Purines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D015398:Signal Transduction; D014230:Triazoles / Q000627:therapeutic use
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D011685:Purine Nucleotides; D011687:Purines; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2; D014230:Triazoles; C111599:istradefylline; C539997:2-(2-furanyl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)-1-piperazinyl)ethyl)-7H-pyrazolo(4,3-e)(1,2,4)triazolo(1,5-c)pyrimidine-5-amine; D000241:Adenosine
keywords: ATP receptors; Adenosine receptor antagonist; Adenosine receptors; GPCR heteromer; Parkinson's disease