Exploiting the anti-inflammatory effects of AMP-activated protein kinase activation.
BACKGROUND
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.


METHODS
The authors provide a background to AMPK signaling and describe the pro-inflammatory signaling pathways and processes shown to be regulated by AMPK activation.


CONCLUSIONS
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.
University of Glasgow, Institute of Cardiovascular & Medical Sciences, College of Medical, Veterinary & Life Sciences, Glasgow G12 8QQ, Scotland, UK.
Ian P
IP
Salt
Timothy M
TM
Palmer
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D004789:Enzyme Activation; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D008659:Metabolic Diseases / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D055372:AMP-Activated Protein Kinases