DOI: 10.1073/pnas.0837397100. Cyclooxygenase-2 is instrumental in Parkinson's disease neurodegeneration

Cyclooxygenase-2 is instrumental in Parkinson's disease neurodegeneration

10.1073/pnas.0837397100

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder of uncertain pathogenesis characterized by the loss of the nigrostriatal dopaminergic neurons, which can be modeled by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Increased expression of cyclooxygenase type 2 (COX-2) and production of prostaglandin E 2 have been implicated in neurodegeneration in several pathological settings. Here we show that COX-2, the rate-limiting enzyme in prostaglandin E 2 synthesis, is up-regulated in brain dopaminergic neurons of both PD and MPTP mice. COX-2 induction occurs through a JNK/c-Jun-dependent mechanism after MPTP administration. We demonstrate that targeting COX-2 does not protect against MPTP-induced dopaminergic neurodegeneration by mitigating inflammation. Instead, we provide evidence that COX-2 inhibition prevents the formation of the oxidant species dopamine-quinone, which has been implicated in the pathogenesis of PD. This study supports a critical role for COX-2 in both the pathogenesis and selectivity of the PD neurodegenerative process. Because of the safety record of the COX-2 inhibitors, and their ability to penetrate the blood–brain barrier, these drugs may be therapies for PD.

Bibliography

Teismann, P., Tieu, K., Choi, D.-K., Wu, D.-C., Naini, A., Hunot, S., Vila, M., Jackson-Lewis, V., & Przedborski, S. (2003). Cyclooxygenase-2 is instrumental in Parkinsonâs disease neurodegeneration. Proceedings of the National Academy of Sciences, 100(9), 5473â5478.

Authors 9

Peter Teismann (first)
Kim Tieu (additional)
Dong-Kug Choi (additional)
Du-Chu Wu (additional)
Ali Naini (additional)
Stéphane Hunot (additional)
Miquel Vila (additional)
Vernice Jackson-Lewis (additional)
Serge Przedborski (additional)

References 28 Referenced 527

S Fahn, S Przedborski Merritt's Neurology, ed L P Rowland (Lippincott, Williams & Wilkins, New York), pp. 679–693 (2000). / Merritt's Neurology by Fahn S (2000)
S Przedborski, V Kostic, N Giladi, D Eidelberg Dopamine Receptors and Transporters, eds A Sidhu, M Laruelle, P Vernier (Dekker, New York), pp. 363–402 (2003). / Dopamine Receptors and Transporters by Przedborski S (2003)
10.1038/79661
10.1002/1531-8249(20010201)49:2<176::AID-ANA37>3.0.CO;2-X
10.1523/JNEUROSCI.21-20-08198.2001
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10.1074/jbc.273.16.9886
10.1074/jbc.274.48.34141
10.1074/jbc.273.49.32943
S Przedborski, V Jackson-Lewis, R Djaldetti, G Liberatore, M Vila, S Vukosavic, G Almer Restor Neurol Neurosci 16, 135–142 (2000). / Restor Neurol Neurosci by Przedborski S (2000)
M V Kindt, R E Heikkila, W J Nicklas J Pharmacol Exp Ther 242, 858–863 (1987). / J Pharmacol Exp Ther by Kindt M V (1987)
10.1038/70978
10.1046/j.1471-4159.1995.64020919.x
10.1002/1098-2396(200102)39:2<167::AID-SYN8>3.0.CO;2-U
10.1016/S0304-3940(02)00704-8
10.1073/pnas.162468699
10.1046/j.1471-4159.2000.0751200.x
10.1124/jpet.301.2.494
S Przedborski, V Jackson-Lewis Free Radicals in Brain Pathophysiology, eds G Poli, E Cadenas, L Packer (Dekker, New York), pp. 273–290 (2000). / Free Radicals in Brain Pathophysiology by Przedborski S (2000)
10.1016/0163-7258(91)90054-P
10.1046/j.1471-4159.1999.0731309.x
10.1126/science.1063522

Dates

Type	When
Created	22 years, 4 months ago (April 29, 2003, 12:23 p.m.)
Deposited	3 years, 4 months ago (April 25, 2022, 10 p.m.)
Indexed	3 days, 15 hours ago (Aug. 31, 2025, 6:12 a.m.)
Issued	22 years, 4 months ago (April 17, 2003)
Published	22 years, 4 months ago (April 17, 2003)
Published Online	22 years, 4 months ago (April 17, 2003)
Published Print	22 years, 4 months ago (April 29, 2003)

Funders 0

None

BibTeX

@article{Teismann_2003, title={Cyclooxygenase-2 is instrumental in Parkinson’s disease neurodegeneration}, volume={100}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0837397100}, DOI={10.1073/pnas.0837397100}, number={9}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Teismann, Peter and Tieu, Kim and Choi, Dong-Kug and Wu, Du-Chu and Naini, Ali and Hunot, Stéphane and Vila, Miquel and Jackson-Lewis, Vernice and Przedborski, Serge}, year={2003}, month=apr, pages={5473–5478} }

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