Researchers discover gene crucial for nerve cell insulation

[Guest guest]

Researchers discover gene crucial for nerve cell insulation

http://www.eurekalert.org/pub_releases/2007-04/nioc-rdg041607.php

Researchers funded by the National Institutes of Health have

discovered how a defect in a single master gene disrupts the process

by which several genes interact to create myelin, a fatty coating

that covers nerve cells and increases the speed and reliability of

their electrical signals.

The discovery has implications for understanding disorders of myelin

production. These disorders can affect the peripheral nervous system—

the nerves outside the brain and spine. These disorders are known

collectively as peripheral neuropathies. Peripheral neuropathies can

result in numbness, weakness, pain, and impaired movement. They

include one of the most common genetically inherited disorders,

Charcot-Marie-Tooth disease, which causes progressive muscle

weakening.

The myelin sheath that surrounds a nerve cell is analogous to the

insulating material that coats an electrical cord or wire, keeping

nerve impulses from dissipating, allowing them to travel farther and

faster along the length of the nerve cell.

The researchers discovered how a defect in just one copy of the

gene, known as early growth response gene 2 (EGR2) affects the

normal copy of the gene as well as the functioning of other genes,

resulting in peripheral neuropathy.

" The researchers have deciphered a key sequence essential to the

assembly of myelin, " said Duane , M.D., Director of the

NICHD, the NIH institute that funded the study. " Their discovery

will provide important insight into the origins of disorders

affecting myelin production. "

The study appears in the online version of Molecular and Cellular

Biology.

Svaren, Ph.D., an associate professor in the Department of

Comparative Bioscience at the University of Wisconsin–Madison's

School of Veterinary Medicine, worked with colleagues E.

LeBlanc, and M. Ward, to conduct the study. Dr. Svaren is an

affiliate of NICHD-funded mental retardation and developmental

disabilities research center at the Waisman Center at the University

of Wisconsin.

Until this discovery, researchers did not fully understand the

complex genetic process that enables Schwann cells, found in the

peripheral nervous system, to coat nerves with myelin.

The Newly Discovered Role of EGR2

During this study, the scientists found that EGR2 produces a protein

that activates several other genes necessary for myelin production.

Some of these genes contain the information needed to make

peripheral myelin protein 22 (PMP-22) and myelin protein zero (MPZ).

MPZ is the most abundant protein in myelin in the peripheral nervous

system.

The overproduction or underproduction of the proteins PMP22 and MPZ

account for the majority of inherited peripheral neuropathies, Dr.

Svaren said.

Ultimately, the sequence of activating genes " switches on " the

Schwann cell, which wraps the nerve axon, the arm-like projection

that conveys nerve impulses, in a myelin sheath.

The scientists' research also resolved a long-standing mystery

surrounding why a single mutant copy of the EGR2 gene disrupts the

functioning of the normal EGR2 gene, leading to a disorder of the

nervous system.

In many genetic conditions, the unaffected copy of an affected gene

continues to produce its protein. However, the researchers found

that the mutant EGR2 copy interferes with the interaction between

the normal EGR2 gene and another myelin gene, SOX10, as the two try

to work together to produce the myelin protein MPZ.

Therapeutic Potential

By understanding the process which creates myelin, researchers may

now be able to investigate new therapies for disorders affecting

myelin.

" Our research has uncovered a whole new mechanism for regulating

myelin genes, " said Dr. Svaren. " Our hope is to exploit this

knowledge so that we can adjust the levels of myelin genes such as

PMP22 and MPZ, and thereby create an effective treatment for myelin

diseases. "

Understanding the process by which nerve cells are myelinated also

could be applied to other disorders as well, Dr. Svaren said.

Diabetic neuropathy, which results in a loss of feeling in the

extremities, also is thought to involve myelin production.

Dr. Svaren added that it is possible that the current study's

findings about myelin production in the peripheral nervous system

could lead to greater understanding of how myelination takes place

in the central nervous system (the brain and spinal cord).

Myelination in the central nervous system is not well understood.

Multiple sclerosis, a degenerative muscular disorder that can be

fatal, results from the destruction of myelin in the central nervous

system.

[Guest guest]

Hello everyone:

Maybe I am wrong (it happens sometimes)but is this discovery not a

cure or very close. Well I am just jumping for joy (figuratively).

Yes, yes, its still years away, but 10 years ago I was very depressed

because doctors would just say you will never walk again, there is no

treatment and no cure. 10 years later and see what happens.

Even the 4 years with the advances have been amazing.

5 to 10 more years? HMMM!

Take care