Journal
EXPERT OPINION ON INVESTIGATIONAL DRUGS
Volume 21, Issue 8, Pages 1155-1167Publisher
INFORMA HEALTHCARE
DOI: 10.1517/13543784.2012.696609
Keywords
AMP-activated protein kinase; inflammation; JAK-STAT; MAP kinases; NF-kappa B
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Funding
- Diabetes UK
- British Heart Foundation
- NHS Greater Glasgow and Clyde
- British Heart Foundation [PG/12/1/29276] Funding Source: researchfish
- Diabetes UK [11/0004403] Funding Source: researchfish
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Introduction: AMP-activated protein kinase (AMPK) is the downstream component of a serine/threonine protein kinase cascade involved in the regulation of metabolism. Many studies have also revealed that AMPK activation can exert significant anti-inflammatory and immunosuppressive effects in a variety of cell types and models of inflammatory/autoimmune disease. Because metformin, an AMPK activator that is a favored first-line therapeutic option for type 2 diabetes, may confer benefits in chronic inflammatory diseases and cancers independent of its ability to normalize blood glucose, there is now considerable interest in identifying and exploiting AMPK's anti-inflammatory effects. Areas covered: The authors provide a background to AMPK signaling and describe the pro-inflammatory signaling pathways and processes shown to be regulated by AMPK activation. Expert opinion: Identification of AMPK subunits responsible for specific anti-inflammatory effects, and a molecular understanding of the mechanisms involved, will be necessary to exploit AMPK pathway activation in acute and chronic inflammatory disease settings while minimizing adverse reactions due to deregulation of AMPK's wide-ranging effects on metabolism.
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