TY  - JOUR
A1  - Rajendran, Ranjithkumar
A1  - Böttiger, Gregor
A1  - Stadelmann, Christine
A1  - Karnati, Srikanth
A1  - Berghoff, Martin
T1  - FGF/FGFR pathways in multiple sclerosis and in its disease models
T2  - Cells
N2  - 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.
KW  - FGF
KW  - FGFR
KW  - multiple sclerosis
KW  - EAE
KW  - ERK
KW  - Akt
KW  - BDNF
KW  - LINGO-1
KW  - SEMA3A
Y1  - 2021
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/23659
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-236594
SN  - 2073-4409
VL  - 10
IS  - 4
ER  -