Phospholipid synthesis as a therapeutic target to promote brain repair in MS patients. (R-13641)

Failure of remyelination, the formation of new myelin sheaths surrounding axons, is considered to underlie the progressive nature of demyelinating disorders such as multiple sclerosis (MS). To date, however, there are no therapeutic agents that can effectively induce or enhance myelin regeneration in these disorders. Emerging evidence indicates that subtle changes in cellular and tissular lipid levels and metabolism have a major impact on the formation of myelin-forming oligodendrocytes and remyelination. In support of this notion, our exciting preliminary data indicate that imbalances in the level and metabolism of phospholipids, a major lipid component of myelin membranes, are closely associated with failure of remyelination. Therefore, we hypothesize that phospholipid synthesis and uptake are essential for oligodendrocyte formation and remyelination. By using innovative state-of-the-art lipidomic and transcriptomic approaches, preclinical animal models, and postmortem human brain tissue, we here aim to identify phospholipid metabolism as a novel therapeutic target to promote remyelination, and to provide detailed insight into lipid function in progressive demyelinating disorders such as MS. All in all, findings from this study will lead to the identification of novel clinically-relevant strategies to promote brain repair in neurological disorders such as MS.

Keywords:multiple sclerosis, oligodendrocyte, phospholipids, remyelination

Disciplines:Autoimmunity, Neurological and neuromuscular diseases