Researchers discover a protein responsible for shaping the nervous system
TORONTO - A team of researchers led by The Hospital for Sick Children
(SickKids), the University of Toronto (U of T) and Cold Spring Harbor
Laboratory have discovered a protein that is responsible for shaping the
nervous system. This research was made possible with the support of a
$1.5-million NeuroScience Canada Brain Repair Program team grant that enabled
scientists from across Canada to work together and fast track their research.
This research is reported in the December 8, 2005 issue of the journal Neuron.
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"We discovered that p63 is the major death-promoting protein for nerve cells
during fetal and post-natal development," said Dr. David Kaplan, the paper's
senior author, senior scientist at SickKids, professor of Molecular Genetics,
Medical Genetics & Microbiology at U of T, Canada Research Chair in Cancer and
Neuroscience, and co-team leader on the NeuroScience Canada Brain Repair
Program grant with Dr. Freda Miller of SickKids. "Proteins such as p63 that
regulate beneficial cell death processes during development may cause adverse
affects later in life by making us more sensitive to injury and disease."
At birth, the nervous system has twice the number of nerve cells than needed.
The body disposes of the excess cells by eliminating those that go to the wrong
place or form weak or improper connections. If this process does not happen,
the nervous system cannot function properly. The expression of the p63 protein
guides the nervous system in disposing of the ineffective nerve cells. The
protein is from the p53 family of tumour suppressor proteins that is mutated in
many human cancers.
While p63 is involved in determining which nerve cells die, the research team
also suspects that it determines whether nerve cells die when injured or in
neurological and neurodegenerative diseases such as Alzheimer's and Parkinson's
diseases.
"The discovery of this new protein represents hope for thousands of people
affected by neurological and neurodegenerative disorders, such as multiple
sclerosis, Parkinson's, Alzheimer's and schizophrenia, as well as spinal cord
injury," says the Honourable Michael H. Wilson, Chair of NeuroScience Canada, a
national umbrella organization for neuroscience research, whose Brain Repair
Program helped support this research. "Because this protein is responsible for
the death of nervous systems cells, understanding how we could inhibit its
functions could represent survival for many patients across Canada."
Ten million Canadians of all ages will be affected by a disease, disorder or
injury of the brain, spinal cord or nervous system. These conditions number
more than 1,000. Fifty per cent of all Canadians - about 15 million people -
have had a brain disorder impact their family. Based on Health Canada data, the
economic burden of these disorders is conservatively estimated at 14 per cent
of the total burden of disease, or $22.7 billion annually; however, when
disability is included, the economic burden reaches 38 per cent or more,
according to the World Health Organization.
However, despite the magnitude of the problem, neuroscience research, with
just $100 million total in operating grants in Canada annually, is still
greatly under funded in this country.
To this end, future research for the research team involves testing whether
p63 is the key protein that determines whether nerve cells die when injured or
in neurodegenerative diseases, and will identify drugs that will prevent p63
from functioning that may be used to treat these conditions.
Other members of the research team include Dr. Freda Miller, Canada Research
Chair in Developmental Neurobiology, Dr. W. Bradley Jacobs, Daniel Ho and Dr.
Fanie Barnabe-Heider, all from SickKids, Dr. William Keyes and Dr. Alea Mills
from Cold Spring Harbor Laboratory in Cold Spring Harbor, New York, and Dr.
Jasvinder Atwal and Dr. Gregory Govani of Dr.
Miller's and Kaplan's former group from McGill University.
This research was also supported by the Canadian Institutes of Health
Research, the National Science and Engineering Research Council of Canada, a
McGill Major Studentship, a McGill Tomlinson fellowship, the Canada Research
Chairs Program and SickKids Foundation.
Founded in 1988, NeuroScience Canada is Canada's umbrella organization and
voice for the neurosciences. Through partnering with the public, private and
voluntary sectors, NeuroScience Canada connects the knowledge and resources
available in this area to accelerate neuroscience research and funding, and
maximize the output of Canada's world-class scientists and researchers. The
mission of NeuroScience Canada's Brain Repair Program is to fast-track
neuroscience research in order to develop treatments and therapies more
quickly. Through the Brain Repair Program, NeuroScience Canada and its donors
and partners have already invested $4.5 million to research teams conducting
breakthrough work in the area of brain repair.
The goal of the Brain Repair Program is to initially fund five teams, for a
total investment of $8 million.
The Hospital for Sick Children, affiliated with the University of Toronto, is
Canada's most research-intensive hospital and the largest centre dedicated to
improving children's health in the country. Its mission is to provide the best
in family-centred, compassionate care, to lead in scientific and clinical
advancement, and to prepare the next generation of leaders in child health. For
more information, please visit www.sickkids.ca.
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For more information, please contact:
Chelsea Gay, Public Affairs
The Hospital for Sick Children
(416) 813 5045
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