Researchers from The Hospital for Sick Children (SickKids) and Sunnybrook Health Sciences Centre have identified a receptor (a structure on the surface of the cell that binds to specific proteins) called p75NTR that prevents these nerves from regenerating in the adult nervous system. The study is published in the March 28 advance online edition of Nature Neuroscience.
During childhood development, the body makes nerve connections whereby axons (long fibres of nerve cells) connect with other nerve cells. Sometimes we can make too many of these connections, prompting the body to get rid of the excess axons through a natural process called axon degeneration. The SickKids research team had previously identified a protein, the p75NTR receptor as an important component of this process in the developing child’s brain. More recently, this team set out to find what role this receptor plays in the adult brain.
“The results surprised all of us. We found that when put into play, these receptors didn’t just prevent regeneration – they actively killed axons,” says Dr. Freda Miller, the study’s co-principal investigator, a Senior Scientist at SickKids and Professor in the Department of Molecular Genetics at the University of Toronto. “If this is an active process and we can understand the network of proteins involved, we could intervene and prevent the axons from being destroyed.”
One in three Canadians (approximately 10 million) will be affected by a disease, disorder or injury of the brain, spinal cord or nervous system at some point in their lives. The inability for axons to regenerate not only affects treatment of these conditions, it plays a key role in diseases such as multiple sclerosis, diabetic neuropathy and Alzheimer’s disease.
According to Miller, their work shows that axon degeneration is an ongoing process in the adult central nervous system. She believes it is meant to naturally protect the brain, so that when the wrong circuits are setup, corrections can be made. When the process gets out of control, diseases and disorders can ensue.
“Now that we have identified this receptor the next step is to determine how it actually kills axons,” says co-principal investigator Dr. David Kaplan, a Senior Scientist at SickKids and Professor in the Department of Molecular Genetics at the University of Toronto. “Once we understand this mechanism, we can investigate whether we can rescue axons from degeneration in the injured or diseased nervous system using this information.”
The Hospital for Sick Children (SickKids) is recognized as one of the world’s foremost paediatric health-care institutions and is Canada’s leading centre dedicated to advancing children’s health through the integration of patient care, research and education. Founded in 1875 and affiliated with the University of Toronto, SickKids is one of Canada’s most research-intensive hospitals and has generated discoveries that have helped children globally. Its mission is to provide the best in complex and specialized family-centred care; pioneer scientific and clinical advancements; share expertise; foster an academic environment that nurtures health-care professionals; and champion an accessible, comprehensive and sustainable child health system. SickKids is proud of its vision of Healthier Children. A Better World.™ For more information, please visit www.sickkids.ca.
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