May 29, 2003
A new discovery by scientists at the Montreal Neurological Institute at McGill University may provide insights into multiple sclerosis.
In a study published in the Journal of Neuroscience (2003;23:3735-3744), Dr. Tim Kennedy and colleagues have discovered that a protein called netrin-1 directs the normal movement of the cells that become oligodendrocytes in the developing spinal cord.
Oligodendrocytes are the cells that provide critical support for the nerve cells - they make myelin, the electrical insulation of the central nervous system. They are also the cells that degenerate and die in multiple sclerosis (MS). Although oligodendrocytes play an essential role in the nervous system, many aspects of their basic cell biology are not well understood, which is one of the reasons why MS is such a mystery. This research finding identifies a fundamental mechanism that directs migrating oligodendrocyte precursor cells. This has implications for understanding demyelinating diseases such as MS, where even a small myelin deficit can lead to functional impairment of the nerve cell.
"Dr. Kennedy's research will contribute to the growing body of knowledge which is developing new therapies for MS," said Dr. William McIlroy, MS Society of Canada national medical advisor.
"In order to treat a disease in the most effective way possible, it is necessary to understand the manner in which proteins function," said Dr. Alan Bernstein, president of the Canadian Institutes of Health Research. "Kennedy's discovery is a vital step in understanding the root causes of MS and will play a role in one day developing an entirely new generation of drugs to combat this condition."
It is widely known that netrins are proteins that guide nerve cell axons to their target in the developing nervous system. In the embryo, this can involve axons traveling long distances. "In addition to this long-range function, last year we reported that netrin-1 may have a short-range function associated with the cell surface that contributes to the maintenance of nerve cell-oligodendrocyte interactions in the mature nervous system. This prompted us to study the possibility that netrin-1 might contribute to oligodendrocyte development," said Kennedy, MNI researcher and codiscoverer of netrins.
The researchers showed that netrin acts as a repellent cue for migrating oligodendrocytes - directing them to move away from sources of netrin. "This result was very exciting for us because netrins are ancient signposts in developing nervous systems," said Kennedy. "They've been pointing axons in the right direction for at least 500 million years. Although 500 million years ago very simple animals did exist - like little worms - oligodendrocytes had not yet evolved. Evolution has been suggested to work like someone who tinkers with bits and pieces to make new things, like pasting together bits and pieces of other pictures to make a new image. In the natural history of oligodendrocyte cell biology, netrin is an example of something that was already there doing other things, that got picked up along the way and applied to a new purpose."
"Understanding the basic biology of oligodendrocytes is very important for MS. If we can understand what stimulates them to function, then perhaps we can develop new targets for therapy," explained Dr. Jack Antel, a neurologist at the Montreal Neurological Institute specializing in the research and treatment of MS.
This research was supported by the Canadian Institutes of Health Research
(CIHR) and the Multiple Sclerosis Society of Canada. This article was prepared
by Pain and Central Nervous System Week editors from staff and other reports.
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