Linking energy sensing to suppression of JAK-STAT signalling: A potential route for repurposing AMPK activators?
Pharmacol Res
; 128: 88-100, 2018 02.
Article
em En
| MEDLINE
| ID: mdl-29037480
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.
Palavras-chave
A769662 (PubChem CID: 54708532); AICAR (PubChem CID: 17513); AMP-activated protein kinase; Anagrelide (PubChem CID: 2182); Aspirin (PubChem CID: 2244); Busulfan (PubChem CID: 2478); Ciclosporin (PubChem CID: 5284373); Fludarabine (PubChem CID: 3367); Hydroxyurea (PubChem CID: 3657); Janus kinase; Lymphoma; Metformin (PubChem CID: 4091); Methotrexate (PubChem CID: 126941); Myeloproliferative neoplasms; Rheumatoid arthritis; Ruxolitinib (PubChem CID: 25126798); Salicylate (PubChem CID:338); Sulfasalazine (PubChem CID: 5359476); Tofacitinib (PubChem CID: 9926791)
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição STAT
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Janus Quinases
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Proteínas Quinases Ativadas por AMP
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article