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Defective movement of cell's power plants implicated in commom inherited neurological disorder

WASHINGTON, DC, January 16, 2007 Contrary to previous thinking, the inefficient movement of cell's "power plants" - the mitochondria - within a cell, rather than their low energy production, may be a contributing factor in the development of Charcot-Marie-Tooth disease (CMT), new research shows.

The study, published in the January 10 issue of The Journal of Neuroscience, is the first to show that mutations in the gene Mitofusin 2 (MFN2), known to cause a form of CMT, also disrupt the movement of the cell's mitochondria, which deliver energy within the cell. A minor disruption in mitochondria movement reduces the energy supply, weakening or even killing the cell.

In CMT, which affects 1 in 2,500 individuals, nerves and muscles in the feet and hands weaken, causing numbness and, in many cases, the loss of function. CMT affects peripheral nerves, among the longest nerves in the body where energy transport is vital.

"This work is of critical importance because the design of effective therapeutic approaches requires an understanding of the underlying disease mechanism," says Brian Popko, PhD, professor in neurological diseases at the University of Chicago who is not connected to the study.

The new research also provides strong evidence that effective energy transportation is key to long cell life, according to senior author Robert H. Baloh, PhD, at the Washington University School of Medicine.

Using rat tissue, Baloh and colleagues removed neurons similar to those affected in CMT patients. They then inserted mutant MFN2 genes in the nucleus of those cells using engineered viruses. Time-lapse videos were taken with a fluorescent microscope in order to observe the speed at which the mitochondria moved. In normal cells, mitochondria are highly mobile. However, in the neurons with mutant MFN2 genes, movement is significantly reduced.

Still unknown is exactly how the mutated MFN2 protein alters mitochondri
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Contact: Sara Harris
sharris@sfn.org
202-962-4000
Society for Neuroscience
16-Jan-2007


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