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A Role for the Non-Receptor Tyrosine Kinase Abl2/Arg in Experimental Neuroinflammation

Aksel Jacobsen, Freja, Scherer, Alexander N., Mouritsen, Jeppe, Bragadóttir, Hera, Bäckström, B. Thomas, Sardar, Samra, Holmberg, Dan, Koleske, Anthony J., Andersson, Åsa
2018

Article in journal (Refereegranskat)

Abstract:

Multiple sclerosis is a neuroinflammatory degenerative disease, caused by activated immune cells infiltrating the CNS. The disease etiology involves both genetic and environmental factors. The mouse genetic locus, Eae27, linked to disease development in the experimental autoimmune encephalomyelitis (EAE) model for multiple sclerosis, was studied in order to identify contributing disease susceptibility factors and potential drug targets for multiple sclerosis. Studies of an Eae27 congenic mouse strain, revealed that genetic variation within Eae27 influences EAE development. The Abl2 gene, encoding the non-receptor tyrosine kinase Arg, is located in the 4,1 megabase pair long Eae27 region. The Arg protein plays an important role in cellular regulation and is, in addition, involved in signaling through the B- and T-cell receptors, important for the autoimmune response. The presence of a single nucleotide polymorphism causing an amino acid change in a near actin-interacting domain of Arg, in addition to altered lymphocyte activation in the congenic mice upon immunization with myelin antigen, makes Abl2/Arg a candidate gene for EAE. Here we demonstrate that the non-synonymous SNP does not change Arg’s binding affinity for F-actin but suggest a role for Abl kinases in CNS inflammation pathogenesis by showing that pharmacological inhibition of Abl kinases ameliorates EAE, but not experimental arthritis. © 2018 The Author(s)

Key words: Abl kinase; Arg; Eae27; Experimental autoimmune encephalomyelitis; Imatinib

Cite: Aksel Jacobsen, Freja, Scherer, Alexander N., Mouritsen, Jeppe, Bragadóttir, Hera, Bäckström, B. Thomas, Sardar, Samra, Holmberg, Dan, Koleske, Anthony J., Andersson, Åsa, Jacobsen, Freja Aksel & Thomas Bäckström, B., A Role for the Non-Receptor Tyrosine Kinase Abl2/Arg in Experimental Neuroinflammation, Journal of Neuroimmune Pharmacology., 13:2, s. 265-276, 2018https://doi.org/10.1007/s11481-018-9783-8