FGF/FGFR pathways in multiple sclerosis and in its disease models

Please always quote using this URN: urn:nbn:de:bvb:20-opus-236594
  • 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; FGF1Multiple 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.show moreshow less

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar Statistics
Metadaten
Author: Ranjithkumar Rajendran, Gregor Böttiger, Christine Stadelmann, Srikanth Karnati, Martin Berghoff
URN:urn:nbn:de:bvb:20-opus-236594
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Anatomie und Zellbiologie
Language:English
Parent Title (English):Cells
ISSN:2073-4409
Year of Completion:2021
Volume:10
Issue:4
Article Number:884
Source:Cells (2021) 10:4, 884. https://doi.org/10.3390/cells10040884
DOI:https://doi.org/10.3390/cells10040884
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:Akt; BDNF; EAE; ERK; FGF; FGFR; LINGO-1; SEMA3A; multiple sclerosis
Release Date:2022/08/10
Date of first Publication:2021/04/13
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International