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

Authors :
Jacobsen, Freja Aksel
Scherer, Alexander N.
Mouritsen, Jeppe
Bragadóttir, Hera
Thomas Bäckström, B.
Sardar, Samra
Holmberg, Dan
Koleske, Anthony J.
Andersson, Åsa
Source :
Journal of NeuroImmune Pharmacology; Jun2018, Vol. 13 Issue 2, p265-276, 12p
Publication Year :
2018

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, <italic>Eae27</italic>, 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 <italic>Eae27</italic> congenic mouse strain, revealed that genetic variation within <italic>Eae27</italic> influences EAE development. The <italic>Abl2</italic> gene, encoding the non-receptor tyrosine kinase Arg, is located in the 4,1 megabase pair long <italic>Eae27</italic> 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 <italic>Abl2/Arg</italic> 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
15571890
Volume :
13
Issue :
2
Database :
Complementary Index
Journal :
Journal of NeuroImmune Pharmacology
Publication Type :
Academic Journal
Accession number :
129370594
Full Text :
https://doi.org/10.1007/s11481-018-9783-8