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February 14, 1994
Media Contact:Joann Rodgers
Phone: (410) 955-8659
E-mail:
JRodgers@welchlink.welch.jhu.edu
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.