Development of protein kinase activators: AMPK as a target in metabolic disorders and cancer.
AMP-activated protein kinase (AMPK) is a cellular energy sensor activated by metabolic stresses that either inhibit ATP synthesis or accelerate ATP consumption. Activation of AMPK in response to an increase in the cellular AMP:ATP ratio results in inhibition of ATP-consuming processes such as gluconeogenesis and fatty acid synthesis, while stimulating ATP-generating processes, including fatty acid oxidation. These alterations in lipid and glucose metabolism would be expected to ameliorate the pathogenesis of obesity, type 2 diabetes and other metabolic disorders. Recently, AMPK has also been identified as a potential target for cancer prevention and/or treatment. Cell growth and proliferation are energetically demanding, and AMPK may act as an "energy checkpoint" that permits growth and proliferation only when energy reserves are sufficient. Thus, activators of AMPK could have potential as novel therapeutics both for metabolic disorders and for cancer, which together constitute two of the most prevalent groups of diseases worldwide.
Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
S
S
Fogarty
D G
DG
Hardie
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D004734:Energy Metabolism / Q000187:drug effects; D020536:Enzyme Activators / Q000737:chemistry / Q000627:therapeutic use*; D005227:Fatty Acids / Q000096:biosynthesis / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects; D006801:Humans; D008659:Metabolic Diseases / Q000188:drug therapy* / Q000201:enzymology; D009369:Neoplasms / Q000201:enzymology / Q000517:prevention & control*
D020536:Enzyme Activators; D005227:Fatty Acids; D000255:Adenosine Triphosphate; D055372:AMP-Activated Protein Kinases