Project R-9179

Fatty acid metabolism in control of the phenotype of foamy phagocytes in multiple sclerosis. (Research)

Multiple sclerosis (MS) is a neurodegenerative autoimmune disease of the central nervous system in which microglia and infiltrated macrophages play a crucial role. Driving these phagocytes towards an anti-inflammatory and regenerative phenotype is considered a promising strategy to halt MS disease progression. Despite being the most abundant cell type in MS lesions, the impact that myelin-containing phagocytes have on MS lesion progression remains largely unclear. My preliminary data now indicate that prolonged intracellular accumulation of myelin-derived lipids skews phagocytes towards a disease-promoting phenotype. Moreover, I found that an enzyme involved in fatty acid metabolism plays a key role in the induction of this phenotype. By using well-established animal models for neuroinflammation and CNS repair, I unravel in this project whether inhibitors of this enzyme represent a promising therapeutic intervention for MS. Furthermore, I define if this enzyme also drives the phenotype of human mye-phagocytes and unravel the molecular mechanisms that underlie the impact that it has on the phenotype of mye-phagocytes. Obtained results will lead to increased insight into MS lesion development and repair, and identify modulators of fatty acid metabolism as promising therapeutic interventions for MS.

01 October 2018 - 30 September 2021