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RING finger protein 5 may guide treatment for muscle disease in older adults
Date:4/4/2008

Researchers at the Burnham Institute for Medical Research (Burnham) have discovered a new player in the development of a disorder called Sporadic Inclusion Body Myositis (sIBM). sIBM is a muscle disease that affects predominantly older men, causing muscles to gradually weaken and waste away. The number of people living with sIBM is unknown, but it is the most common muscle disease among those over the age of 50, and due to its unfamiliarity, it is probably underdiagnosed. This discovery provides a potential avenue for future diagnostic and therapeutic opportunities for this disease.

In muscles, proteins are continuously made and broken down by the endoplasmic reticulum (ER), a protein factory in the cell. To assure that proteins produced pass quality control, a set of ER-based inspectors identify and remove those proteins that are not properly folded. Ubiquitin ligase RNF5 (or RING Finger Protein 5) acts much like one of these quality-control inspectors at the end of the assembly line by tagging defective protein products so that they can be recycled. Burnham scientists have found that RNF5 plays a key role in the progression of IBM. While the causes of sIBM or how it progresses are still mostly unknown, and there is no cure or standard treatment, this finding offers a new understanding for the mechanism underlying development of sIBM and points to possible use of new markers for diagnosis and mouse models to test for novel therapeutics. The results of this study appeared in PLoS ONE on February 13.

The Burnham research team was led by Zeev Ronai, Ph.D., and included Agnes Delaunay, PhD., and P. Lorenzo Puri, M.D., Ph.D., with Diane Shelton, D.V.M. Ph.D of UCSD and international collaborators from Japan and Italy. Dr. Ronai had previously shown that RNF5 is important for muscle maintenance in the worm model C. elegans; now the team discovered that RNF5 is up-regulated in biopsies from sIBM patients.

Following this discovery, the
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Contact: Andrea Moser
amoser@burnham.org
858-646-3146
Burnham Institute
Source:Eurekalert  

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