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

Speirs, C., Williams, J. J.L., Riches, K., Salt, I. P. and Palmer, T. M. (2018) Linking energy sensing to suppression of JAK-STAT signalling: a potential route for repurposing AMPK activators? Pharmacological Research, 128, pp. 88-100. (doi:10.1016/j.phrs.2017.10.001) (PMID:29037480)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Williams, Dr Jamie and Salt, Dr Ian and Speirs, Miss Claire and Palmer, Dr Tim
Authors: Speirs, C., Williams, J. J.L., Riches, K., Salt, I. P., and Palmer, T. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Pharmacological Research
Publisher:Elsevier
ISSN:1043-6618
ISSN (Online):1096-1186
Published Online:13 October 2017
Copyright Holders:Copyright © 2017 Elsevier Ltd.
First Published:First published in Pharmacological Research 128:88-108
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
641891Inhibition of endothelial mitogen-activated protein kinases by amp-activated protein kinaseIan SaltBritish Heart Foundation (BHF)PG/13/82/30483RI CARDIOVASCULAR & MEDICAL SCIENCES
655031"SUPPRESSION OF IL-6 TRANS-SIGNALLING BY BMP4:A "MISSING LINK" IN THE DEVELOPMENT OF PULMONARY ARTERIAL HYPERTENSION?"Timothy PalmerBritish Heart Foundation (BHF)PG/14/32/30812RI CARDIOVASCULAR & MEDICAL SCIENCES
605941Extracellular signal-regulated kinase 5 (ERK5) and regulation of neuroendocrine differentiation in prostate cancerTimothy PalmerChief Scientist office (CSO)ETM/226RI CARDIOVASCULAR & MEDICAL SCIENCES
591651Reversal of endothelial interleukin-6 signalling in by AMPK: a new mechanism underlying increased cardiovascular disease risk and identification of new drug targets.Timothy PalmerNHS Greater Glasgow and Clyde (NHSGGC)2011REFCH08RI CARDIOVASCULAR & MEDICAL SCIENCES