Altered Lipid Metabolism in CNS Demyelination and Remyelination Are Key Elements Driving Progressive MS

Lipids, together with water and proteins, constitute the essential structure of cell membranes, and in the CNS, critically contribute to the production, function, and maintenance of the myelin sheath. Myelin produced by oligodendrocytes (OLs) acts as an electric insulator and assures proper conduction of information. Three major fractions of myelin lipids are cholesterol, phospholipids, and glycolipids. These lipids not only sculpt the myelin landscape as a structural support for proteins, but they also play a crucial role in molecular interactions underlying processes of protein trafficking and signal transductions. The high lipid content of myelin makes it susceptible to lipid metabolism disorders. Disorders in systemic and local lipid metabolism may lead to loss of myelin integrity and stability, and potentially to CNS demyelination seen in neurodegenerative diseases, notably progressive multiple sclerosis, for which there are few effective therapies. Precise interactions among disorders in lipid metabolism, function of oligodendrocytes, and demyelination/remyelination events, including de novo myelin formation and myelin remodeling processes, may lay the foundation for novel therapeutics for progressive MS and other demyelinating CNS conditions.