COX-2 Enzyme Instrumental In Parkinson's Disease

COX-2 enzymes are more familiar in arthritis, but the enzymes produce inflammation in all damaged tissues, including the brain. Many researchers now see the inflammation as a critical process in neurodegenerative diseases, and studies have shown that non-steroidal anti-inflammatory drugs (NSAIDS) reduce the risk of developing Alzheimer's disease.

To see if COX-2 plays a role in Parkinson's disease, Dr. Serge Przedborski, professor of neurology and pathology in the College of Physicians & Surgeons and faculty member in the Columbia University Center for Neurobiology and Behavior, and postdoctoral researcher Dr. Peter Teismann looked for the enzyme in postmortem brains of Parkinson's patients. They found higher levels of COX-2 in the dopamine neurons of patients than in the neurons of brains without the disease. Dopamine neurons suffer the most damage from the disease.

The researchers then tested the importance of COX-2 in mice that have a disease similar to Parkinson's. The mice have the same high level of COX-2 in their dopamine neurons as patients do, making the mouse a valuable model for studying the human disease.

COX-2 was found to have an instrumental role in the death of the neurons. When the COX-2 enzyme was removed from the mice, or inhibited with a COX-2 inhibitor, more dopamine neurons were able to survive. Rofecoxib, the COX-2 inhibitor, doubled the number of surviving neurons: 88 percent survived with the drug, while only 41 percent survived without the drug.

Surprisingly, however, the COX-2 enzyme does not kill neurons through inflammation. When the enzyme was removed from mice or inhibited with a drug, the researchers did not see the reduction in inflammation they expected to see.

Instead, they found that the COX-2 enzyme may kill by oxidizing other molecules in the dopamine neurons. The oxidized molecules then react with and damage other components of the cell. Excessive damage can kill the cell.

Many researchers have hypothesized that oxidative damage kills neurons in Parkinson's disease.

"Regardless of how COX-2 works in Parkinson's disease, the benefit we see in animal models with COX-2 inhibitors suggests the drugs could be useful in slowing the disease's progression in patients," Dr. Przedborski says. "The drugs are safe and they get into the brain reasonably well."

The National Institute on Aging sponsors a multi-center trial testing COX-2 inhibitors in Alzheimer's patients. Dr. Przedborski says researchers are planning new trials to test the drug in Parkinson's patients.

This study was funded, in part, by grants from the National institutes of Health/National Institute of Neurological Disorders and Stroke, the U.S. Department of Defense, and the Parkinson's Disease Foundation, New York.