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A Role for the Non-...
A Role for the Non-Receptor Tyrosine Kinase Abl2/Arg in Experimental Neuroinflammation
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- Aksel Jacobsen, Freja (author)
- University of Copenhagen, Copenhagen, Denmark & Novo Nordisk A/S, Bagsværd, Denmark
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- Scherer, Alexander N. (author)
- Yale University School of Medicine, New Haven, CT, USA
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- Mouritsen, Jeppe (author)
- University of Copenhagen, Copenhagen, Denmark & Novozymes A/S, Bagsværd, Denmark
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- Bragadóttir, Hera (author)
- University of Copenhagen, Copenhagen, Denmark & Xelia Pharmaceuticals A/S, Copenhagen, Denmark
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- Bäckström, B. Thomas (author)
- Novo Nordisk A/S, Måløv, Denmark & BTB Pharma, Malmö, Sweden
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- Sardar, Samra (author)
- University of Copenhagen, Copenhagen, Denmark
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- Holmberg, Dan (author)
- Lund University,Lunds universitet,Autoimmunitet,Forskargrupper vid Lunds universitet,Autoimmunity,Lund University Research Groups,Lund University, Malmö, Sweden
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- Koleske, Anthony J. (author)
- Yale University School of Medicine, New Haven, CT, USA
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- Andersson, Åsa, 1960- (author)
- Halmstad University,Högskolan i Halmstad,Rydberglaboratoriet för tillämpad naturvetenskap (RLAS),University of Copenhagen, Copenhagen, Denmark
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(creator_code:org_t)
- 2018-03-17
- 2018
- English.
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In: Journal of Neuroimmune Pharmacology. - New York, NY : Springer-Verlag New York. - 1557-1890 .- 1557-1904. ; 13:2, s. 265-276
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Abstract
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- 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)
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Keyword
- Abl kinase
- Arg
- Eae27
- Experimental autoimmune encephalomyelitis
- Imatinib
- Abl kinase
- Arg
- Eae27
- Experimental autoimmune encephalomyelitis
- Imatinib
Publication and Content Type
- ref (subject category)
- art (subject category)
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Aksel Jacobsen, ...
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Scherer, Alexand ...
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Mouritsen, Jeppe
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Bragadóttir, Her ...
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Bäckström, B. Th ...
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Sardar, Samra
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Holmberg, Dan
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Koleske, Anthony ...
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Andersson, Åsa, ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Rheumatology and ...
- Articles in the publication
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Journal of Neuro ...
- By the university
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Halmstad University
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Lund University