Format

Send to

Choose Destination
J Neuroimmune Pharmacol. 2018 Jun;13(2):265-276. doi: 10.1007/s11481-018-9783-8. Epub 2018 Mar 17.

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

Author information

1
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
2
Novo Nordisk A/S, Bagsværd, Denmark.
3
Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA.
4
Novozymes A/S, Bagsværd, Denmark.
5
Xellia Pharmaceuticals A/S, Copenhagen, Denmark.
6
Novo Nordisk A/S, Måløv, Denmark.
7
BTB Pharma, Malmö, Sweden.
8
Autoimmunity section, CRC, Lund University, Malmö, Sweden.
9
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT, USA.
10
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. asa.andersson@hh.se.
11
Rydberg laboratories for Applied Science, Academy of Business, Technology and Science, University of Halmstad, Halmstad, Sweden. asa.andersson@hh.se.

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.

KEYWORDS:

Abl kinase; Arg; Eae27; Experimental autoimmune encephalomyelitis; Imatinib

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center