We will define if impaired lipophagy in phagocytes promotes the accumulation of myelin-derived lipids, and if inducing lipophagy enhances repair, suppresses neuroinflammation, and presents a therapeutic target in MS.

Multiple sclerosis (MS) is a neurodegenerative autoimmune disease in which microglia and infiltrated macrophages play a crucial role. Our data indicate that prolonged intracellular accumulation of myelin-derived lipids skews phagocytes towards a disease-promoting phenotype. We found that lipophagy, is implicated in this phenotype. Using in vitro and animal models of neuroinflammation and remyelination, we will unravel the mechanisms that underlie the degradation of lipid droplets by lipophagy in phagocytes, and determine whether targeting lipophagy represents an effective therapeutic intervention. Obtained results will lead to increased insight into MS lesion development and repair, and may identify lipophagy inducers as promising therapeutics in MS.