About 3,000 people in Denmark suffer from one of the serious muscle-related diseases that come under the heading of muscular dystrophy. Some patients diagnosed with muscular dystrophy die shortly after birth, others become severely retarded and develop eye problems, while certain groups are confined to life in a wheelchair. Common to all muscular dystrophy sufferers is the difficulty of their muscle cells to attach themselves to each other and to the surrounding tissue. However, little is actually known about the root causes of the disease.
New basic research from University of Copenhagen now offers insight into previously unknown facts about muscular dystrophy that may improve future diagnosis and treatment of the disease. The findings have just been published in the scientific journal PNAS (Proceedings of the National Academy of Science).
"Our new research findings may shed light on some of the cellular processes that take place in connection with, for example, muscular dystrophy. This is important information because it is crucial for us to gain as detailed an understanding as possible about the individual cell components. Although the journey from the current basic research to any potential treatment options or diagnostic tools is a long one, our discoveries give grounds for optimism," says postdoc Malene Bech Vester-Christensen - who carried out the new experiments from her base at the Faculty of Health and Medical Sciences, University of Copenhagen, and has since taken up a research position at Novo Nordisk.
Sugar molecules central to our organism
The new method developed by researchers makes it easier to map the proteins that The protein previously associated with muscular dystrophy is a so-called glycoprotein - a protein with chains of sugar molecules attached. The special kind of sugar attached to these glycoproteins is called mannose. A functional pathway for binding mannose to the proteins is key to the functioning of the human organism, and genetic defects in the process that attaches mannose to the proteins - known as O-mannosylation - can lead to diseases such as muscular dystrophy.
"To date, only one single protein has been identified and characterised where the mannose deficiency on the protein leads to muscular dystrophy, but our method enables us to faster identify many new proteins that have mannose attached and therefore potentially play a key role for the disease," says Adnan Halim, who is associated with the research project and a postdoc with the Danish National Research Foundation, Copenhagen Center for Glycomics.
Vester-Christensen MB, Halim A, Joshi HJ, Steentoft C, Bennett EP, Levery SB, Vakhrushev SY, Clausen H. Mining the O-mannose glycoproteome reveals cadherins as major O-mannosylated glycoproteins. Proc Natl Acad Sci U S A. 2013 Oct 7.