A new study has revealed that the glycoprotein “contactin-1” is essential for myelination of the central nervous system (CNS). The findings, published in PNAS, will guide novel approaches aimed to regenerate myelin for patients with multiple sclerosis (MS) and other myelin-degenerating diseases.
Using a combination of molecular biology, electron microscopy, and genetically engineered mice, Barbara Ranscht, Ph.D., professor in Sanford-Burnham’s NCI-Designated Cancer Center and Tumor Microenvironment Program, led her team to reveal multiple, interrelated roles of contactin-1 in CNS myelination.
“Now we know that contactin-1 is essential to produce the myelin in the CNS—in addition to attaching it to the axons like in the periphery,” said Ranscht. “This is relevant because MS is a disease that specifically destroys the myelin in the CNS—and contactin-1 is key to where regeneration of myelin needs to happen.”
Myelin has a vital role in controlling functions of the nervous system. Neurons connect with other neurons through spindle-shaped processes called axons that carry information in form of electrical signals to other neurons. To make this information flow efficiently and to keep neurons healthy, many axons are insulated by a white fatty substance called myelin—similar to the plastic coating around an electrical wire.
When myelin is damaged, signals are transmitted more slowly, and over time may be blocked completely as axons are affected.
Deciphering the molecular signals exchanged between axons and oligodendrocytes—the myelin-generating cells in the CNS—is an essential step toward finding strategies for repairing damaged myelin in diseases like MS.
“We look forward to studies exploring how contactin-1 is expressed in MS lesions in mouse and human tissue samples.” Oligodendrocytes are present around myelin lesions in MS patients, but they fail to myelinate. “We are interested to know if contactin-1 is needed to trigger new myelin production not only during development as shown in our current study, but also in repairing damaged myelin in disease,” said Ranscht.
Other authors of the paper include Gülsen Çolakoğlu, Ulrika Bergstrom-Tyberg, and Erik Berglund from the Ranscht lab.
MS is a chronic, often disabling disease that attacks the CNS. MS is an immune-mediated disease that damages the myelin, forming scar tissue.
Symptoms of MS are unpredictable and vary from one person to the other. Some people experience abnormal fatigue and episodes of numbing and tingling. Others have a loss of balance and muscle coordination, making it difficult to walk. Slurred speech, tremors, stiffness, and bladder problems are also common.
More than 2.3 million people are affected by MS worldwide. There is no cure for MS, but there are FDA-approved medications that “modify” or slow down the course of MS.
Advances in treating and understanding MS are made every year, and progress to find a cure is very encouraging.
To see the San Diego Union Tribune coverage of this story: http://www.utsandiego.com/news/2013/Dec/30/ranscht-colakoglu-myelin-contactin/
Full copy of paper: http://www.pnas.org/content/early/2014/01/02/1313769110.long