New Way To Stimulate Brain To Release Antioxidants - Burnham Institute
For Medical Research
Category: Neurology/Neuroscience News
Article Date: 10 Jan 2006

A joint research effort between researchers at the Burnham Institute
for Medical Research in La Jolla, CA, and a team from Japan (Iwate
University, Osaka City University, Gifu University, Iwate Medical
University) has discovered a novel way to treat stroke and
neurodegenerative disorders. This approach works by inducing nerve
cells in the brain and the spine to release natural antioxidants that
protect nerve cells from stress and free radicals that lead to
neurodegenerative diseases. Until this discovery, researchers were
unable to induce release of these specific antioxidants directly in
nerve cells, at the site where damage and degeneration occurs.

In stroke and various neurodegenerative disorders, such as Alzheimer's
disease and Lou Gehrig's disease, glutamate, an amino acid found in
high quantities in the brain, is thought to accumulate. At normal
concentrations, glutamate acts as a neurotransmitter that nerves use to
communicate. However, at excessive levels glutamate is toxic, resulting
in over stimulation of nerve cells, known as excitotoxicity, and
causing excessive stress on the nerve cells eventually ending in cell
death. Studies described in this report suggest that NEPPs (short for
NEurite outgrowth-Promoting Prostaglandins), compounds that accumulate
in nerve cells, prevent nerve damage by activating the Keap1/Nrf2
pathway that regulates the production of antioxidants which relieve
cells of damaging free radicals that result from excitotoxicity.

"This is the first reported evidence that this protective response can
be activated directly in nerve cells to release antioxidants and
counter oxidative stress," said Stuart Lipton, M.D., Ph.D., Director of
the Del E. Webb Center for Neurosciences and Aging at the Burnham
Institute and senior author of the study. "These findings provide
support for further investigation of NEPP drugs to potentially treat
ischemic stroke, multiple sclerosis, Alzheimer's disease, Lou Gehrig's
disease and other neurodegenerative disorders."

Researchers found that NEPPs were able to activate a pathway in nerve
cells that is designed to protect against oxidative and nitrosative
stress (which produces free radicals) and excitotoxicity. This pathway,
known as Keap1/NrF2, regulates the production of natural antioxidants,
such as bilirubin, that can protect against oxidative stress resulting
from ischemic stroke and degenerative disorders.

A paper detailing the findings of this study, entitled "Activation of
the Keap1/Nrf2 Pathway for Neuroprotection by Electrophilic Phase II
Inducers" (Satoh, et al.), will be published in the January 17th issue
of the Proceeding of the National Academy of Sciences. In addition, the
findings will be made available by expedited publication at the
journal's website on January 10th.This research was supported with
grants from the National Institutes of Health.

About the Burnham Institute for Medical Research

The Burnham Institute for Medical Research, founded in 1976, is an
independent not-for-profit biomedical research institution dedicated to
advancing the frontiers of scientific knowledge and providing the
foundation for tomorrow's medical therapies. The Institute is home to
three major centers: the Cancer Center, the Del E. Webb Neuroscience
and Aging Center, and the Infectious and Inflammatory Disease Center.
Since 1981, the Institute's Cancer Center has been a member of the
National Cancer Institute's prestigious Cancer Centers program.
Discoveries by Burnham scientists have contributed to the development
of new drugs for Alzheimer's disease, heart disease and several forms
of cancer. Today the Institute employs over 725, including more than
550 scientists. The majority of the Institute's funding derives from
federal sources, but private philanthropic support is essential to
continuing bold and innovative research. For additional information
about the Institute and ways to support the research efforts of the
Institute, visit http://www.burnham.org.

Nancy Beddingfield
nbeddingfield@burnham.org
Burnham Institute
http://www.burnham-inst.org

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