Researchers at San Diego's Burnham Institute have discovered a new player in the death of brain cells in such degenerative ailments as Alzheimer's, multiple sclerosis, Lou Gehrig's disease and stroke.

The scientists, whose work is profiled Friday in the journal Science , found that nitric oxide gas in the body can activate enzymes that chew up the outside surfaces of nerve cells, destroying the cells.

Scientists have long been looking inside nerve cells to find out why the normal process of cell death, called apoptosis, can go haywire, killing too many cells in the case of many degenerative diseases, or not enough, which can lead to cancer. The Burnham Institute study, which examined the brain cells of mice, was the first to describe how nitric oxide can activate enzymes, called matrix metalloproteinases, or MMPs, outside cells. "People have known that MMPs were activated in multiple sclerosis, Alzheimer's, stroke, (and) in HIV-related dementia, so they knew that somehow MMPs might be important to these diseases," said Burnham Institute neurologist Stuart Lipton, who led the study.
Scientists had not known, however, that nitric oxide could activate these MMP enzymes, Lipton said.

Identifying nitric oxide as a catalyst for cell death may lead to new drugs to inhibit the influence of nitric oxide on the MMP enzymes, increasing the medicines available for degenerative brain diseases, Lipton said.

When they operate properly, MMP enzymes reduce inflammation, so it will be critical that new drugs target the cause of disease.

"If you make a drug that's too good, then you block the normal function of the brain," Lipton said.

Scientists had already found that elevated levels of nitric oxide can harm nerve cells, but they had not known that the gas triggered MMP enzymes in disease.
"The exact mechanism whereby nitric oxide does this hadn't been (identified)" before Lipton's study, said Solomon Synder, director of the Department of Neuroscience at Johns Hopkins University School of Medicine in Maryland.
Lipton's study "was very original work," Snyder said.

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