Fibrinogen Leakage as a Cause of Reduced Myelin Production in the Aging Brain

Myelin sheaths nerves, and is essential to their function. Demyelinating conditions in which myelin is lost are debilitating and ultimately fatal. We all lose myelin to some degree over the course of aging, however. This is thought to contribute to age-related cognitive decline, among other aspects of aging. The researchers here identify a mechanism that causes this loss, and it arises as a consequence of the progressive age-related dysfunction of the blood-brain barrier, intended to seal away the biochemistry of the central nervous system from the biochemistry of the rest of the body. As this barrier breaks down, allowing leakage of various proteins and other molecules into the brain, all sorts of inappropriate and unwanted changes in cellular behavior can take place, such as in the cells responsible for maintaining myelin.

Picture a bare wire, without its regular plastic coating. It's exposed to the elements and risks being degraded. And, without insulation, it may not conduct electricity as well as a coated wire. Now, imagine this wire is inside your brain. Much like that bare wire, the nerve fibers in the brain lose their protective coating, called myelin, and become extremely vulnerable. This leaves the nerve cells exposed to their environment and reduces their ability to transmit signals quickly, resulting in impaired cognition, sensation, and movement. In disease, the brain seems to activate mechanisms to repair myelin, but cannot complete the process. For years, scientists have been trying to understand why these repair mechanisms are halted, as overcoming this obstacle holds great potential for treating disabling neurological diseases.

The cells needed to repair myelin already exist in the central nervous system. They are adult stem cells that travel to sites of damage, where they mature into myelin-producing cells. However, in many neurological diseases, this process is blocked. This is why the brain is unable to repair damaged myelin. In an effort to understand why the brain can't repair itself, scientists have in the past focused on understanding what happens inside the cell. "We thought it might be important to look instead at the toxic environment outside the cell, where blood proteins accumulate. We found that when fibrinogen (a blood-clotting protein) leaks into the central nervous system, it stops brain cells from producing myelin and, as a result, prevents repair. We realized that targeting the blood protein fibrinogen could open up the possibility for new types of therapies to promote brain repair."

"Repairing myelin by eliminating the toxic effects of blood-brain barrier dysfunction in the brain is a new frontier in disease therapeutics." Researchers can now look for new ways to target fibrinogen as a way to restore regenerative functions in the central nervous system. This could lead to novel therapies to help patients with multiple sclerosis and many other diseases associated with myelin.


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