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Penn Researchers Prove "Short-Cut" Function Of Myelin Sheath Channel: BetterUnderstanding Of Myelin Should Lead To Therapies For Neuropathies

Diseases of the covering of nerve cells -- called the myelin sheath -- can be quite debilitating and affect hundreds of thousands of people each year. Multiple sclerosis, which afflicts nerve cells in the brain, is one of the most well known. As part of a long-term investigation, researchers at the University of Pennsylvania Medical Center have demonstrated for the first time how a biochemical channel important for the exchange of cell nutrients links the multiple layers of myelin to the outside space.

"This is a big breakthrough for understanding how myelin works, with implications for all demyelinating diseases, including multiple sclerosis," says Steven Scherer, MD, PhD, associate professor of neurology, who collaborated with Rita Balice-Gordon, PhD, assistant professor of neuroscience, and former Penn combined degree student Linda J. Bone, MD, PhD, on this study.

In earlier work, mutations in components of the channel were associated with inherited forms of neuropathies. Specifically, five years ago, former Penn neurologist Kenneth H. Fischbeck, MD, and Scherer reported that mutations in connexin32 -- a protein found in myelin-producing as well as other cells -- cause X-linked Charcot-Marie-Tooth disease (CMTX), a genetic disorder that produces progressive degeneration of peripheral nerves. One out of 3,000 people suffer from Charcot-Marie-Tooth disease, with 10 to 20 percent of those having this particular inherited form. This led the research team to reappraise the function of connexin32 in myelinating cells. They hypothesized that connexin32 forms part of a six-sided channel wall -- called the gap junction -- that couples the multiple layers of the sheath to the outside, extracellular space. "Our most recent work directly demonstrates the channel's function in the myelin sheath for the first time," says Scherer. The researchers report their findings in the August 24 issue of the Journal of Cell Biology.

The myelin sheat
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Contact: Karen Young Kreeger
kreeger@mail.med.upenn.edu
(215) 614-0290
University of Pennsylvania School of Medicine
24-Aug-1998


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