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Review
. 2021 Apr 13;10(4):884.
doi: 10.3390/cells10040884.

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

Ranjithkumar Rajendran  1 , Gregor Böttiger  1 , Christine Stadelmann  2 , Srikanth Karnati  3 , Martin Berghoff  1
Affiliations
Review

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

Ranjithkumar Rajendran et al. Cells. .

Abstract

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS) affecting more than two million people worldwide. In MS, oligodendrocytes and myelin sheaths are destroyed by autoimmune-mediated inflammation, while remyelination is impaired. Recent investigations of post-mortem tissue suggest that Fibroblast growth factor (FGF) signaling may regulate inflammation and myelination in MS. FGF2 expression seems to correlate positively with macrophages/microglia and negatively with myelination; FGF1 was suggested to promote remyelination. In myelin oligodendrocyte glycoprotein (MOG)35-55-induced experimental autoimmune encephalomyelitis (EAE), systemic deletion of FGF2 suggested that FGF2 may promote remyelination. Specific deletion of FGF receptors (FGFRs) in oligodendrocytes in this EAE model resulted in a decrease of lymphocyte and macrophage/microglia infiltration as well as myelin and axon degeneration. These effects were mediated by ERK/Akt phosphorylation, a brain-derived neurotrophic factor, and downregulation of inhibitors of remyelination. In the first part of this review, the most important pharmacotherapeutic principles for MS will be illustrated, and then we will review recent advances made on FGF signaling in MS. Thus, we will suggest application of FGFR inhibitors, which are currently used in Phase II and III cancer trials, as a therapeutic option to reduce inflammation and induce remyelination in EAE and eventually MS.

Keywords: Akt; BDNF; EAE; ERK; FGF; FGFR; LINGO-1; SEMA3A; multiple sclerosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Lesion types and FGF/FGFR expression in multiple sclerosis. Depending on the lesion type, FGFs are associated with myelin damage and inflammation to a varying degree. Abundancy is especially high in acutely demyelinating lesions.
Figure 2
Figure 2
Effects of oligodendrocyte-specific deletion of FGFR1 and FGFR2 in EAE. Proposed neuroprotective and anti-inflammatory mechanisms of oligodendrocyte-specific deletion of FGFR1 (dark grey arrows) and FGFR2 (bright grey arrows) in MOG35-55-induced EAE (according to [108] and [109]).
See this image and copyright information in PMC

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