Linking energy sensing to suppression of JAK-STAT signalling: A potential route for repurposing AMPK activators?

[Display omitted] Exaggerated Janus kinase-signal transducer and activator of transcription (JAK-STAT) signalling is key to the pathogenesis of pro-inflammatory disorders, such as rheumatoid arthritis and cardiovascular diseases. Mutational activation of JAKs is also responsible for several haematol...

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Bibliographic Details
Published in:Pharmacological research 2018-02, Vol.128, p.88-100
Main Authors: Speirs, Claire, Williams, Jamie J.L., Riches, Kirsten, Salt, Ian P., Palmer, Timothy M.
Format: Article
Language:English
Subjects:
AMP-activated protein kinase
AMP-Activated Protein Kinases - metabolism
Animals
Humans
Inflammation - metabolism
Interleukin-6 - metabolism
Janus kinase
Janus Kinases - metabolism
Lymphoma
Myeloproliferative neoplasms
Rheumatoid arthritis
Signal Transduction
STAT Transcription Factors - metabolism
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Summary:[Display omitted] Exaggerated Janus kinase-signal transducer and activator of transcription (JAK-STAT) signalling is key to the pathogenesis of pro-inflammatory disorders, such as rheumatoid arthritis and cardiovascular diseases. Mutational activation of JAKs is also responsible for several haematological malignancies, including myeloproliferative neoplasms and acute lymphoblastic leukaemia. Accumulating evidence links adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK), an energy sensor and regulator of organismal and cellular metabolism, with the suppression of immune and inflammatory processes. Recent studies have shown that activation of AMPK can limit JAK-STAT-dependent signalling pathways via several mechanisms. These novel findings support AMPK activation as a strategy for management of an array of disorders characterised by hyper-activation of the JAK-STAT pathway. This review discusses the pivotal role of JAK-STAT signalling in a range of disorders and how both established clinically used and novel AMPK activators might be used to treat these conditions.
ISSN:1043-6618
1096-1186
DOI:10.1016/j.phrs.2017.10.001