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Background  Accumulating evidence has shown that the inflammatory process participates in the pathogenesis of amyotrophic lateral sclerosis (ALS), suggesting a therapeutic potential of anti-inflammatory agents. Janus kinase 2 (JAK2), one of the key molecules in inflammation, transduces signals downstream of various inflammatory cytokines, and some Janus kinase inhibitors have already been clinically applied to the treatment of inflammatory diseases. However, the efficacy of JAK2 inhibitors in treatment of ALS remains to be demonstrated. In this study, we examined the role of JAK2 in ALS by administering a selective JAK2 inhibitor, R723, to an animal model of ALS (mSOD1 G93A  mice).    Findings  Orally administered R723 had sufficient access to spinal cord tissue of mSOD1 G93A  mice and significantly reduced the number of  Ly6c positive  blood monocytes, as well as the expression levels of IFN-γ and nitric oxide synthase 2, inducible (iNOS) in the spinal cord tissue. R723 treatment did not alter the expression levels of Il-1β, Il-6, TNF, and NADPH oxidase 2 (NOX2), and suppressed the expression of Retnla, which is one of the markers of neuroprotective M2 microglia. As a result, R723 did not alter disease progression or survival of mSOD1 G93A  mice.    Conclusions  JAK2 inhibitor was not effective against ALS symptoms in mSOD1 G93A  mice, irrespective of suppression in several inflammatory molecules. Simultaneous suppression of  anti-inflammatory microglia  with a failure to inhibit critical other inflammatory molecules might explain this result.    Electronic supplementary material  The online version of this article (doi:10.1186/s12974-014-0179-2) contains supplementary material, which is available to authorized users.

journal of neuroinflammation

Partial suppression of M1 microglia by Janus kinase 2 inhibitor does not protect against neurodegeneration in animal models of amyotrophic lateral sclerosis