Researchers discover a protein responsible for shaping the nervous system

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 ProgramTM 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.

“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.