Abstract
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, characterized by demyelination and neurodegeneration. Despite significant research efforts, the exact mechanisms driving MS pathology remain incompletely understood. The Vanden Berghe lab provided evidence that ferroptosis—an iron-dependent form of regulated cell death— contributes to MS pathogenesis, and its pharmacological inhibition suppresses experimental disease progression. However, the precise role of ferroptosis in MS—which cells are affected and the resulting consequences—remains poorly understood. This project aims to investigate ferroptosis at the cellular level in MS, identifying its impact on oligodendrocytes, neurons, microglia, astrocytes, and infiltrating immune cells. By integrating neurospheroid cultures, in vivo disease models, and comparing our findings with patient-derived data, we seek to elucidate how ferroptosis contributes to MS pathology. Additionally, the mode of action of ferroptosis inhibition will be evaluated to determine whether its effects are mediated through direct interactions with brain-resident cells or via immune modulation. By investigating ferroptosis at the cellular level, this project will enhance our understanding of MS disease mechanisms, allow a more precise evaluation of its therapeutic potential and might uncover novel therapeutic strategies.
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