Louisville, Ky. – The interaction of a cellular substance known as TWEAK and a cellular receptor to which TWEAK is drawn, can hasten the weakening of muscle that is caused by disuse, a common and potentially deadly complication of many diseases, including heart disease, cystic fibrosis and cancer.
A team of researchers led by Ashok Kumar, Ph.D., of the University of Louisville’s Department of Anatomical Sciences and Neurobiology, will publish these findings in the March 22, 2010 issue of the Journal of Cell Biology. The study was funded by the National Institutes of Health.
“This finding, related to the interaction between TWEAK and a receptor called Fn14 is very important because it has implications for potential drug therapies that might use this interaction as a target,” Kumar said. “Muscle wasting is not only a concern related to many chronic conditions, but it is a serious problem afflicting astronauts who spend any length of time in space and often require physical rehabilitation upon return.”
Previously, Kumar and his team studied the activity of TWEAK and the Fn14 receptor in mice and found that overexpression of TWEAK caused increased muscle loss around the time the animals reached six months of age. This finding coincides with what is commonly observed in humans when muscle loss occurs, Kumar said. However, studying what was happening at the cellular level within the animals’ muscle, the researchers were able to identify the TWEAK/ Fn14 connection.
“While TWEAK is always present, its receptor is not expressed in adult skeletal muscle,” Kumar said. “Conditions of inactivity lead to the expression of TWEAK receptor on muscle cells and subsequent binding of TWEAK to the receptor hastens muscle loss. Future studies will help to determine the full range of clinically relevant settings in which the TWEAK/ Fn14 pathway is operative, and in which inhibition of this pathway is sufficient to preserve functional muscle.”
Muscle atrophy as a complication of illness can hasten death by affecting a patient’s ability to fight infection and in some cases rendering patients unable to eat or breathe on their own. It is sometimes treated with steroids but there is currently no widely accepted drug treatment for the condition, Kumar said.
Other investigators involved in this study include Ashwani Mittal, Shephali Bhatnagar, Akhilesh Kumar, Hong Li and Denys Makonchuk of the University of Louisville, and David Glass, Estelle Lach-Triffilieff and Sandrine Wauters of Novartis Institutes for Biomedical Research.