Development of protein kinase activators: AMPK as a target in metabolic disorders and cancer

S. Fogarty, D. G. Hardie

    Research output: Contribution to journalArticle

    265 Citations (Scopus)

    Abstract

    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. (C) 2009 Elsevier B.V. All rights reserved.

    Original languageEnglish
    Pages (from-to)581-591
    Number of pages11
    JournalBiochimica et Biophysica Acta. Proteins and Proteomics
    Volume1804
    Issue number3
    DOIs
    Publication statusPublished - Mar 2010

    Keywords

    • AMPK
    • Activator
    • Metabolic Syndrome
    • Obesity
    • Diabetes
    • Cancer
    • HER-2/NEU TRANSGENIC MICE
    • TUMOR-SUPPRESSOR LKB1
    • RESPIRATORY COMPLEX-I
    • MOUSE SKELETAL-MUSCLE
    • CREB-BINDING-PROTEIN
    • FATTY-ACID OXIDATION
    • GLUCOSE-UPTAKE
    • GLUT4 TRANSLOCATION
    • SIGNALING PATHWAYS
    • AICA RIBOSIDE

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