Gene found that helps nerve cells survive
by preventing cell suicide
Finding may lead to new treatments
for neurologic disease and nerve injury
BOSTON - September 25, 2002 - Why do some nerve cells survive
and regrow after injury while others shrink away and die? A new
discovery by researchers at Massachusetts General Hospital (MGH)
shows that the expression of a particular gene may be responsible
for protecting neurons from death. The results, published in the
September 26 issue of Neuron, could lead the way for new
treatment strategies for a variety of neurological diseases.
"Turning on the gene named Hsp27
could potentially rescue nerve cells in patients with neurodegenerative
conditions such as Lou Gehrig's disease," says principal investigator
Clifford Woolf, MD, PhD, of the Neural Plasticity Research Group
in the Department of Anesthesia and Critical Care at MGH.
Woolf and his colleagues found that young sensory and motor nerve
cells die after injury because the heat shock protein 27 gene (Hsp27)
is not turned on in these cells. In adult cells however, the gene
is expressed. The resulting protein that is produced protects these
mature nerve cells from death following an injury.
"As part of normal development, many more neurons are made
than are needed," says Woolf, who also is Richard J. Kitz Professor
of Anesthesia Research at Harvard Medical School. "So some
must be pruned away by essentially committing cell suicide, a phenomenon
known as programmed cell death. It seems that Hsp27 is turned
off to allow for this normal developmental process."
Woolf explains that once an individual reaches adulthood, nerve
cells in the body are permanent and irreplaceable. "That's
why it's important to have a repair mechanism for older neurons,"
he says. The protein made by the Hsp27 gene blocks cell suicide
from taking place following injury, rescuing injured cells. For
example, cells expressing the Hsp27 protein acquire resistance to
excessive heat, chemical stress, and toxins. Hsp27 directly
inhibits the cellular proteins that trigger programmed cell death.
In laboratory dishes and in rat models, Woolf and his team showed
that, if the Hsp27 gene is delivered to young nerve cells
using gene therapy with viral vectors, the cells are able to survive
injury just as well as older nerve cells. Equally, if the gene is
switched off in adults, those cells will die. "Hopefully, therapy
that prevents cell death by delivering genes like Hsp27 will
someday find its way into the clinic," says Woolf. "Patients
with Lou Gehrig's disease, for example, suffer a progressive death
of their motor neurons leading to paralysis. If Hsp27 were
able to prevent the death of the neurons in these patients, it would
offer the possibility of new therapy, something we plan to test"
The other members of the MGH research team are Susanna Benn, Ph.D,
first author, Joachim Scholz, MD, and Richard Mannion, MD, PhD -
all of the MGH Neural Plasticity Research Group - and Joanna Bakowska,
DVM, PhD, of the Molecular Neurogenetics Unit at MGH. The study
was supported by grants from the National Institutes of Health and
the Alexander von Humboldt Foundation.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of more than $300 million
and major research centers in AIDS, cardiovascular research, cancer,
cutaneous biology, transplantation biology and photomedicine.
In 1994, the MGH joined with Brigham and Women's Hospital to form
Partners HealthCare System, an integrated health care delivery system
comprising the two academic medical centers, specialty and community
hospitals, a network of physician groups and nonacute and home health
Media Contact: Susan
McGreevey , MGH Public Affairs
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