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

Speirs, Claire; Williams, Jamie J. L.; Riches, Kirsten; Salt, Ian P.; Palmer, Timothy M.

Abstract

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.

Citation

Speirs, C., Williams, J. J. L., Riches, K., Salt, I. P., & Palmer, T. M. (2018). Linking energy sensing to suppression of JAK-STAT signalling: A potential route for repurposing AMPK activators?. Pharmacological research : the official journal of the Italian Pharmacological Society, 128, 88-100. https://doi.org/10.1016/j.phrs.2017.10.001

• Journal Article Type: Review
• Acceptance Date: Oct 12, 2017
• Online Publication Date: Oct 13, 2017
• Publication Date: Feb 1, 2018
• Deposit Date: Oct 30, 2018
• Publicly Available Date: Oct 30, 2018
• Journal: Pharmacological Research
• Print ISSN: 1043-6618
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 128
• Pages: 88-100
• DOI: https://doi.org/10.1016/j.phrs.2017.10.001
• Keywords: Pharmacology
• Public URL: https://hull-repository.worktribe.com/output/1137300
• Related Public URLs: http://eprints.gla.ac.uk/149822/
• Additional Information: This article is maintained by: Elsevier; Article Title: Linking energy sensing to suppression of JAK-STAT signalling: A potential route for repurposing AMPK activators?; Journal Title: Pharmacological Research; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.phrs.2017.10.001; Content Type: article; Copyright: © 2018 Elsevier Ltd. All rights reserved.
• Contract Date: Oct 30, 2018