Cholesterol crystals prevent regeneration in central nervous system

January 16, 2018
The regeneration of intact myelin sheaths is necessary for patients to recover from MS relapses. Nevertheless, the body's ability to regenerate myelin decreases with age. A team from the Technical University of Munich has found a possible explanation: Fat derived from myelin, which is not carried away rapidly enough, can trigger chronic inflammation that in turn impedes regeneration. 

Regeneration of myelin is possible, but in MS it falls short. The research team found that after the destruction of myelin, crystalline cholesterol can trigger persistent inflammation which prevents regeneration.

Myelin contains a very high amount of cholesterol. When myelin is destroyed, the cholesterol released has to be removed from the tissue. This is performed by microglia and macrophages, also referred to as phagocytes. They take up the damaged myelin, digest it, and transport the nondigestible remainder out of the cell by transport molecules. However, if too much cholesterol accumulates in the cell, cholesterol can form needle-shaped crystals, which damage the cell. Using a mouse model, the team showed the devastating effect of the crystalline cholesterol: It activates the inflammasome in phagocytes, which results in the release of inflammatory mediators, attracting even more immune cells.

How well the microglia and macrophages did their job was ultimately also dependent on age: the older the mice, the less effective was the clearance of cholesterol and the stronger the chronic inflammation. According to the researchers, when they treated the mice with a medication that helps transport cholesterol out of the cells, inflammation decreased and myelin was regenerated. 

Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, the team wants to investigate whether this mechanism can be used therapeutically to promote regeneration in MS.

The findings were published the journal Science.

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