Research team
Who rusts and who resists? Unveiling ferroptosis at the cellular level in multiple sclerosis.
Abstract
Multiple sclerosis (MS) is a chronic neuroinflammatory disease characterised by demyelination and neurodegeneration, leading to neurological disability. Current immunomodulatory therapies reduce inflammation but fail to prevent progressive neurodegeneration, highlighting an unmet need for neuroprotective strategies. Despite extensive research, the mechanisms driving MS remain incompletely understood. Emerging evidence implicates ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, in MS pathology. Correlative studies suggest that neurons, oligodendrocytes (OLs), microglia, and astrocytes may be affected by ferroptotic stress, yet direct evidence is lacking. Moreover, our lab has shown that pharmacological inhibition of ferroptosis with FXT-001 reduces demyelination and disease progression in preclinical models, but the underlying mechanisms and cell-type-specific effects remain unclear. Using human iPSC-derived quad-partite neurospheroids, OL nanofiber cultures, mouse models, and post-mortem MS patient tissue, we will map cell-specific ferroptotic responses, test whether ferroptosis drives OL loss and demyelination, and dissect FXT-001?s neuroprotective and immunomodulatory mechanisms. By integrating mechanistic studies with therapeutic intervention, this project aims to define ferroptosis? contribution to MS pathology at the cellular level and establish a rational foundation for targeted neuroprotective strategies.Researcher(s)
- Promoter: Vanden Berghe Tom
- Co-promoter: Ponsaerts Peter
- Fellow: Winkelmans Imke
Research team(s)
Funding
- FWO
- FWO
Project type(s)
- Research Project
Who Rusts and Who Resists? Unveiling Ferroptosis at the Cellular Level in Multiple Sclerosis.
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.Researcher(s)
- Promoter: Vanden Berghe Tom
- Co-promoter: Ponsaerts Peter
- Fellow: Winkelmans Imke
Research team(s)
Funding
- BOF
Project type(s)
- Research Project