I take etodolac, which reduces COX-2 (and also, some COX-1, so I take misoprostol with it.) It works great for osteoarthritis. Anyone else on a COX-2 inhibitor?

Neuroscience

PNAS | April 29, 2003 | vol. 100 | no. 9 | 5473-5478


Cyclooxygenase-2 is instrumental in Parkinson's disease neurodegeneration

Peter Teismann*, Kim Tieu*, Dong-Kug Choi*, Du-Chu Wu*, Ali Naini*, Stéphane Hunotdagger , Miquel Vila*, Vernice Jackson-Lewis*, and Serge Przedborski*,Dagger ,§,¶


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 E2 have been implicated in neurodegeneration in several pathological settings.

Here we show that COX-2, the rate-limiting enzyme in prostaglandin E2 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.