QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (76) Citing Articles via Google Scholar Google Scholar Articles by Chen, J.-F. Articles by Schwarzschild, M. A. Search for Related Content PubMed PubMed Citation Articles by Chen, J.-F. Articles by Schwarzschild, M. A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE CAFFEINE DOPAMINE

Next Article 

The Journal of Neuroscience, 2001, 21:RC143:1-6

RAPID COMMUNICATION
Neuroprotection by Caffeine and A_2A Adenosine Receptor Inactivation in a Model of Parkinson's Disease

Jiang-Fan Chen¹, Kui Xu¹, Jacobus P. Petzer², Roland Staal³, Yue-Hang Xu¹, Mark Beilstein¹, Patricia K. Sonsalla³, Kay Castagnoli², Neal Castagnoli Jr², and Michael A. Schwarzschild¹

¹ Molecular Neurobiology Laboratory, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, ² Harvey W. Peters Center, Department of Chemistry, Virginia Tech, Blacksburg, Virginia 24061-0212, and ³ Department of Neurology, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854-5635

Recent epidemiological studies have established an association between the common consumption of coffee or other caffeinated beverages and a reduced risk 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 through 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 typical human exposure, attenuated MPTP-induced loss of striatal dopamine and dopamine transporter binding sites. The effects of caffeine were mimicked by several A_2A antagonists (7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH 58261), 3,7-dimethyl-1-propargylxanthine, and (E)-1,3-diethyl-8 (KW-6002)-(3,4-dimethoxystyryl)-7-methyl-3,7-dihydro-1H-purine-2,6-dione) (KW-6002) and by genetic inactivation of the A_2A receptor, but not by A₁ 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 enhance the potential of A_2A antagonists as a novel treatment for this neurodegenerative disease.

Key words: adenosine receptor; methylxanthine; neurotoxin; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; dopamine transporter; Parkinson's disease; knock-out; mice

---

Copyright © Society for Neuroscience  0270-6474//$05.00/0

This article has been cited by other articles:

				H. Wang, W. Zhang, C. Zhu, C. Bucher, B. R. Blazar, C. Zhang, J.-F. Chen, J. Linden, C. Wu, and Y. Huo Inactivation of the Adenosine A2A Receptor Protects Apolipoprotein E-Deficient Mice From Atherosclerosis Arterioscler Thromb Vasc Biol, July 1, 2009; 29(7): 1046 - 1052. [Abstract] [Full Text] [PDF]

				L. Yu, J. E. Coelho, X. Zhang, Y. Fu, A. Tillman, U. Karaoz, B. B. Fredholm, Z. Weng, and J.-F. Chen Uncovering multiple molecular targets for caffeine using a drug target validation strategy combining A2A receptor knockout mice with microarray profiling Physiol Genomics, May 13, 2009; 37(3): 199 - 210. [Abstract] [Full Text] [PDF]

				L. C. Tan, W.-P. Koh, J.-M. Yuan, R. Wang, W.-L. Au, J. H. Tan, E.-K. Tan, and M. C. Yu Differential Effects of Black versus Green Tea on Risk of Parkinson's Disease in the Singapore Chinese Health Study Am. J. Epidemiol., March 1, 2008; 167(5): 553 - 560. [Abstract] [Full Text] [PDF]

				T. Mihara, K. Mihara, J. Yarimizu, Y. Mitani, R. Matsuda, H. Yamamoto, S. Aoki, A. Akahane, A. Iwashita, and N. Matsuoka Pharmacological Characterization of a Novel, Potent Adenosine A1 and A2A Receptor Dual Antagonist, 5-[5-Amino-3-(4-fluorophenyl)pyrazin-2-yl]-1-isopropylpyridine-2(1H)-one (ASP5854), in Models of Parkinson's Disease and Cognition J. Pharmacol. Exp. Ther., November 1, 2007; 323(2): 708 - 719. [Abstract] [Full Text] [PDF]

				C. E. Hamill, W. M. Caudle, J. R. Richardson, H. Yuan, K. D. Pennell, J. G. Greene, G. W. Miller, and S. F. Traynelis Exacerbation of Dopaminergic Terminal Damage in a Mouse Model of Parkinson's Disease by the G-Protein-Coupled Receptor Protease-Activated Receptor 1 Mol. Pharmacol., September 1, 2007; 72(3): 653 - 664. [Abstract] [Full Text] [PDF]

				K. Xu, Y. Xu, D. Brown-Jermyn, J.-F. Chen, A. Ascherio, D. E. Dluzen, and M. A. Schwarzschild Estrogen Prevents Neuroprotection by Caffeine in the Mouse 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Model of Parkinson's Disease J. Neurosci., January 11, 2006; 26(2): 535 - 541. [Abstract] [Full Text] [PDF]

				H.-Y. Shen, J.-C. He, Y. Wang, Q.-Y. Huang, and J.-F. Chen Geldanamycin Induces Heat Shock Protein 70 and Protects against MPTP-induced Dopaminergic Neurotoxicity in Mice J. Biol. Chem., December 2, 2005; 280(48): 39962 - 39969. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help