In the war against diseases, nerve cells need their armor

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In the war against diseases, nerve cells need their armor

Scientists find key step in maintaining myelin

http://www.eurekalert.org/pub_releases/2008-11/mnia-itw111208.php

In a new study, researchers at the Montreal Neurological Institute

(MNI), McGill University, and the Université de Montréal have

discovered an essential mechanism for the maintenance of the normal

structure of myelin, the protective covering that insulates and

supports nerve cells (neurons). Up until now, very little was known

about myelin maintenance. This new information provides vital insight

into diseases such as Multiple Sclerosis (MS) and other progressive

demyelinating diseases in which myelin is destroyed, causing

irreversible damage and disrupting the nerve cells' ability to

transmit messages. The research, published recently in the Journal of

Neuroscience, is the first to identify a role for the protein netrin-

1, previously characterized only in the developing nervous system,

with this critical function in the adult nervous system. This

research was funded by the MS Society of Canada and the Canadian

Institutes of Health Research.

Netrin-1, a protein deriving its name from the ancient Indian

language, Sanskrit, word for 'one who guides,' is known to guide and

direct nerve cell axons to their targets. In the molecular biological

studies conducted by the team, they found that blocking the function

of netrin-1 and one of its receptors in adult neural tissue causes

the disruption of myelin. " We've known for just over 10 years that

netrin is essential for normal development of the nervous system, and

we also knew that netrin was present in the adult brain, but we

didn't know why. It is fascinating that netrin-1 has such a vital

role in maintaining the structure of myelin in the adult nervous

system, " says Dr. Tim Kennedy, a neuroscientist at the MNI and the

senior investigator of this study, " continuing to pursue the

implications of that are incredibly exciting. " " Our mission is to

find a cure as quickly as possible and enhance quality of life, " says

Lee, assistant vice-president of research programs for the MS

Society of Canada. " We are pleased to be involved in funding work

that supports our mission and feel that this research takes us closer

to understanding the players and processes that could aid in

remyelination. "

The results of this study, a collaboration between Dr. Kennedy's

laboratory, clinician-scientists in the Neuroimmunology group at the

MNI headed by Dr. Jack Antel, and Dr. Di Polo's laboratory at

the Université de Montréal, are especially significant in Canada

which has one of the highest rates of Multiple Sclerosis (MS) in the

world with approximately 1,000 new cases of MS diagnosed each

year. ''This is an exciting new area of research that could lead to

new treatment strategies and ultimately improve the life of the

people who suffer from MS. We are proud to be funding this

collaborative research between basic and clinician-scientists, " said

Dr. Rémi Quirion, Scientific Director of the CIHR Institute of

Neurosciences, Mental Health and Addiction.

MS is a disease of the central nervous system in which myelin is

destroyed. Understanding the factors involved in maintaining myelin

and promoting remyelination, offers new therapeutic targets and

avenues for the treatment of MS. As described by Dr. Jack

Antel, " Current MS therapies aim to block inflammation. In order to

protect and restore myelin it is essential to to understand the

molecules involved in these processes. This is the new era of the

neurobiology of MS. " The team is taking the investigation further by

teaming up with the MS clinic and doctors at the MNI, providing

access to a huge amount of patient data, and enabling them a broader

clinical perspective.

Importantly, this newly discovered mechanism implicates a cascade of

protein molecules that have not been known to be involved in

myelination. The study was carried out in mice and using in vitro

cell cultures. The investigators found that myelin develops normally,

but then begins to come apart. Interestingly, in some respects this

mirrors what happens in some demyelinating diseases like MS, where

myelin forms and may be stable for years, but is then disrupted and

begins to fail. Specifically, the new findings show that netrin-1 and

its receptor are needed to hold paranodal junctions in place, and

thereby maintain the structure of myelin. The paranodal junction is a

highly specialized region of contact where an oligodendrocyte cell

attaches itself to the nerve cell's axon. This juncture acts as a

molecular fence, which organizes and segregates the distribution of

key proteins along the nerve cells axon and plays an imperative role

in the proper conduction of electrical signals along the length of

the nerve cell. When the function of netrin-1 and its receptor is

disrupted, the organization of this adhesive junction comes apart,

disrupting the function of nerve cells in the brain and spinal cord.