The pro-inflammatory environment characteristic of multiple sclerosis (MS) reduces the levels of PPAR-gamma — a receptor protein whose activation dampens inflammation — and impairs myelin processing in immune cells that clear myelin debris, a study suggests.
These findings may help to better understand how PPAR-gamma regulates the function of these immune cells and contributes to MS progression, the researchers noted. They also may identify potential therapeutic targets for the disease.
The study, “Altered PPARγ Expression Promotes Myelin-Induced Foam Cell Formation in Macrophages in Multiple Sclerosis,” was published in the International Journal of Molecular Sciences.
In MS, the immune system mistakenly attacks myelin, the fatty protective sheath that covers nerve fibers. Previous studies have shown that while macrophages, a type of immune cell, contribute to myelin degradation, they also can promote its repair by clearing related debris from the brain and spinal cord.
The uptake of myelin debris by macrophages leads to the transport of cholesterol, its main fatty component, out of the cell, to keep a healthy fat balance within the cell. However, many macrophages containing abundant vesicles of myelin fragments — and presenting a so-called foamy appearance — are found near sites of myelin loss. Of note, vesicles are tiny sacs that transport material within or outside the cell.
Such findings suggest that macrophages’ myelin processing and fat metabolism may be impaired in MS patients. Notably, a previous study showed that sustained accumulation of myelin debris inside macrophages promotes a pro-inflammatory state.
However, the causes of this fat metabolism dysregulation remain largely unclear.
Now, a team of researchers in Belgium, along with colleagues in France and the Netherlands, have shed light on the mechanisms behind fat metabolism deficits in macrophages.
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