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Neuroprotection by adenosine A 2A receptor blockade in experimental models of Parkinson's disease
Author(s) -
Ikeda Ken,
Kurokawa Masako,
Aoyama Shiro,
Kuwana Yoshihisa
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.0022-3042.2001.00694.x
Subject(s) - neuroprotection , adenosine a2a receptor , mptp , dopaminergic , parkinson's disease , pharmacology , dopamine , gliosis , neuroscience , striatum , neurodegeneration , dopamine receptor d2 , receptor , adenosine receptor , medicine , biology , agonist , disease
Adenosine A 2A receptors are abundant in the caudate‐putamen and involved in the motor control in several species. In MPTP‐treated monkeys, A 2A receptor‐blockade with an antagonist alleviates parkinsonian symptoms without provoking dyskinesia, suggesting this receptor may offer a new target for the antisymptomatic therapy of Parkinson's disease. In the present study, a significant neuroprotective effect of A 2A receptor antagonists is shown in experimental models of Parkinson's disease. Oral administration of A 2A receptor antagonists protected against the loss of nigral dopaminergic neuronal cells induced by 6‐hydroxydopamine in rats. A 2A antagonists also prevented the functional loss of dopaminergic nerve terminals in the striatum and the ensuing gliosis caused by MPTP in mice. The neuroprotective property of A 2A receptor antagonists may be exerted by altering the packaging of these neurotoxins into vesicles, thus reducing their effective intracellular concentration. We therefore conclude that the adenosine A 2A receptor may provide a novel target for the long‐term medication of Parkinson's disease, because blockade of this receptor exerts both acutely antisymptomatic and chronically neuroprotective activities.