"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.
For more information, please contact:
Chelsea Gay, Public Affairs
The Hospital for Sick Children
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