Project R-15175

Decoding the Phagocyte Lipidome in Multiple Sclerosis: Targeting ApoE-Associated Changes in the Macrophage and Microglial Lipid metabolism to Promote Remyelination. (Research)

Multiple sclerosis (MS) is a chronic inflammatory demyelinating autoimmune disease affecting the central nervous system (CNS). Existing therapies can alleviate early-stage symptoms but fail to prevent neurodegeneration in the chronic phase, highlighting the urgent need for novel treatments. In MS pathology, macrophages and microglia play a dual role. They can either contribute to disease progression by adopting a pro-inflammatory phenotype and internalizing myelin debris, or promote repair by efficiently clearing damaged myelin. Lipid metabolism, a key factor in shaping the phagocyte phenotype, is influenced by the lipid transporter Apolipoprotein E (ApoE) which modulates CNS lipid homeostasis. Beyond its established association with Alzheimer's Disease, it is increasingly evident that ApoE also plays a crucial role in MS, as the ApoE4 isoform is linked to accelerated disease progression and impaired remyelination. This project aims to unravel the intricate relationship between ApoE isoforms and the phagocyte lipidome, and how this impacts de- and remyelination in MS. The innovative lipidomic and transcriptomic technologies used in this project will uncover new pathways underlying the disease-promoting phenotype of phagocytes and substantially increase our knowledge of the involvement of the phagocyte lipidome and ApoE isoforms in MS pathology. This project will pave the way to novel ApoE genotype-specific therapies targeting lipid metabolism pathways in MS.

01 January 2025 - 31 December 2028