Neuroprotection by caffeine and A(2A) adenosine receptor inactivation in amodel of Parkinson's disease

Citation
Jf. Chen et al., Neuroprotection by caffeine and A(2A) adenosine receptor inactivation in amodel of Parkinson's disease, J NEUROSC, 21(10), 2001, pp. NIL_1-NIL_6
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROSCIENCE
ISSN journal
0270-6474 → ACNP
Volume
21
Issue
10
Year of publication
2001
Pages
NIL_1 - NIL_6
Database
ISI
SICI code
0270-6474(20010515)21:10<NIL_1:NBCAAA>2.0.ZU;2-#
Abstract
Recent epidemiological studies have established an association between the common consumption of coffee or other caffeinated beverages and a reduced r isk of developing Parkinson's disease (PD). To explore the possibility that caffeine helps prevent the dopaminergic deficits characteristic of PD, we investigated the effects of caffeine and the adenosine receptor subtypes th rough which it may act in the 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) neurotoxin model of PD. Caffeine, at doses comparable to those of t ypical human exposure, attenuated MPTP-induced loss of striatal dopamine an d dopamine transporter binding sites. The effects of caffeine were mimicked by several A(2A) antagonists (7-(2-phenylethyl)-5-amino-2-(2- furyl)-pyraz olo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH 58261), 3,7-dimethyl-1-pro pargylxanthine, and (E)-1,3-diethyl-8 (KW-6002)-(3,4-dimethoxystyryl)-7-met hyl-3,7-dihydro-1H-purine-2,6- dione) (KW-6002) and by genetic inactivation of the A2A receptor, but not by A(1) receptor blockade with 8-cyclopentyl- 1,3-dipropylxanthine, suggesting that caffeine attenuates MPTP toxicity by A(2A) receptor blockade. These data establish a potential neural basis for the inverse association of caffeine with the development of PD, and they en hance the potential of A(2A) antagonists as a novel treatment for this neur odegenerative disease.