February 14, 1994
Media Contact:Joann Rodgers
Phone: (410) 955-8659

One reason nerves die prematurely in diseases such as Lou Gehrig's or Parkinson's may be activation of a natural program for death that lives quietly in all cells, according to a study by a team of Hopkins neuroscientists.

Researchers Rajiv Ratan, M.D., Ph.D., Timothy Murphy, Ph.D., and Jay Baraban, M.D., Ph.D., have shown that a condition called oxidative stress, common in nerve-destroying diseases and in spinal cord or brain injuries, puts nerve cells on a preprogrammed spiral into death.

By deciphering a key part of this process, the research sheds light on how nerve diseases may progress and offers possible drug targets for the future. It also may spark new strategies for regenerating lost nerve cells in patients with Parkinson's or Alzheimer's diseases.

The study, in the January Journal of Neurochemical, also is a preliminary step in explaining how the body normally eliminates unwanted cells - especially in embryos.

The research centers on a constant need in cells to "mop up" reactive molecules called free radicals. These highly toxic substances are a natural product of a cell's energy-getting reactions, says Ratan. "Yet, since these molecules are toxic, cells have evolved a very elaborate system to neutralize their effects," he says.

"Problems appear to come," says Ratan, "when some tips the balance between free radical production and the cell's defense" - a situation called oxidative stress. This can kill nerve cells, the researchers say.

Ratan's team studied a model of cell death: cultures of cells from the brains of rat embryos to which they added glutamate, a natural nerve stimulator that, in high concentrations, causes oxidative stress. It also causes death.

Most cells displayed altered chemistry, then the shrinkage and tom-up DNA characteristic of programmed cell death. (This death is different from the sort that happens, say, if cells are deprived of food.)

When the researchers added chemicals that can "mop up" excess free radicals to the model they found no signs of programmed death.

"Programmed cell death occurs all the time as the nervous system develops," says Ratan. "In some parts of embryos, more than 50 percent of the nerve cells die. What we've shown is that the process can be inappropriately unleashed by abnormal stimuli such as those implicated in nerve disease."

"We think that intentional cell death and the sort that come with certain nerve diseases follow the same pathways, but only further work will tell us that," says Ratan. The research was supported by NIH grants.

-- JHMI --
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