AMP-Activated Protein Kinase: A Target for Drugs both Ancient and Modern

D Grahame Hardie (Lead / Corresponding author), Fiona A Ross, Simon A Hawley

    Research output: Contribution to journalReview article

    245 Citations (Scopus)
    152 Downloads (Pure)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)1222-36
    Number of pages15
    JournalChemistry & Biology
    Volume19
    Issue number10
    DOIs
    Publication statusPublished - 26 Oct 2012

    Keywords

    • AMP-Activated Protein Kinases
    • Anti-Bacterial Agents
    • Diabetes Mellitus, Type 2
    • Humans
    • Hypoglycemic Agents
    • Metformin
    • Neoplasms
    • Protein-Serine-Threonine Kinases
    • Salicylates
    • Journal Article
    • Research Support, Non-U.S. Gov't
    • Review

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