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

Exaggerated Janus kinase-signal transducer and activator of transcription (JAKSTAT) 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 JAKSTAT 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.

URI

http://hdl.handle.net/10454/13522

Version

Accepted manuscript

Citation

Speirs C, Williams JJL, Riches-Suman K et al (2017) Linking energy sensing to suppression of JAK-STAT signalling: a potential route for repurposing AMPK activators. Pharmacological Research. 128: 88-100.

Link to Version of Record

https://doi.org/10.1016/j.phrs.2017.10.001

Type

Article