FGF/FGFR Pathways in Multiple Sclerosis and in Its Disease Models.

Area of Science:

• Neuroimmunology
• Neurodegenerative diseases
• Cell signaling

Background:

• Multiple sclerosis (MS) is a chronic CNS disease characterized by inflammation, demyelination, and neurodegeneration.
• Oligodendrocyte and myelin damage is central to MS pathology, with impaired remyelination.
• Fibroblast growth factor (FGF) signaling is implicated in MS, with FGF2 potentially promoting inflammation and FGF1 aiding remyelination.

Purpose of the Study:

• To review the role of FGF signaling in MS.
• To explore the therapeutic potential of targeting FGF signaling pathways for MS treatment.

Main Methods:

• Analysis of post-mortem MS tissue.
• Investigation of FGF2 and FGF1 roles in MOG35-55-induced experimental autoimmune encephalomyelitis (EAE) in mice.
• Specific deletion of FGF receptors (FGFRs) in oligodendrocytes in the EAE model.
• Assessment of inflammatory cell infiltration, myelin and axon integrity, and molecular signaling pathways (ERK/Akt, BDNF).

Main Results:

• FGF2 expression correlated with inflammation and inversely with myelination in MS.
• Targeting FGFRs in oligodendrocytes in EAE reduced inflammation and demyelination.
• FGFR inhibition modulated ERK/Akt phosphorylation, brain-derived neurotrophic factor levels, and remyelination inhibitor expression.

Conclusions:

• FGF signaling plays a complex role in MS pathogenesis, influencing both inflammation and remyelination.
• Inhibitors of FGF receptors (FGFRs), currently in cancer trials, represent a potential therapeutic strategy for MS.
• Targeting FGFRs may reduce CNS inflammation and promote remyelination in MS and EAE models.