JOURNAL ARTICLE
REVIEW

AMP-activated protein kinase: a target for drugs both ancient and modern

D Grahame Hardie, Fiona A Ross, Simon A Hawley
Chemistry & Biology 2012 October 26, 19 (10): 1222-36
23102217
The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status. It is activated, by a mechanism requiring the tumor suppressor LKB1, by metabolic stresses that increase cellular ADP:ATP and/or AMP:ATP ratios. Once activated, it switches on catabolic pathways that generate ATP, while switching off biosynthetic pathways and cell-cycle progress. These effects suggest that AMPK activators might be useful for treatment and/or prevention of type 2 diabetes and cancer. Indeed, AMPK is activated by the drugs metformin and salicylate, the latter being the major breakdown product of aspirin. Metformin is widely used to treat diabetes, while there is epidemiological evidence that both metformin and aspirin provide protection against cancer. We review the mechanisms of AMPK activation by these and other drugs, and by natural products derived from traditional herbal medicines.

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