Journal
NEUROPHARMACOLOGY
Volume 104, Issue -, Pages 161-168Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2015.07.024
Keywords
Adenosine receptors; ATP receptors; Adenosine receptor antagonist; GPCR heteromer; Parkinson's disease
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Funding
- Spanish Ministry of Economy and Competitiveness (MINECO) [SAF2012-39875-C02-01]
- Swedish Medical Research Council [62X-00715-50-3]
- AFA Forsakring [130328]
- Karolinska Institutets Forskningsstiftelser
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Purinergic signaling modulates dopaminergic neurotransmission in health and disease. Classically adenosine A(1) and A(2A) 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 A(2A) receptor antagonist, istradefyiline, 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 P2X(1) 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. (C) 2015 Elsevier Ltd. All rights reserved.
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