Role of 5′-adenosine monophosphate-activated protein kinase in cell survival and death responses in neurons

Petronela Weisová, David Dávila, Liam P. Tuffy, Manus Ward, Caoimhín G. Concannon, Jochen H.M. Prehn

    Research output: Contribution to journalArticlepeer-review

    55 Scopus citations

    Abstract

    5′-Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a key sensor of cellular energy status. AMPK signaling regulates energy balance at the cellular, organ, and whole-body level. More recently, it has become apparent that AMPK plays also an important role in long-term decisions that determine cell fate, in particular cell cycle progression and apoptosis activation. Here, we describe the diverse mechanisms of AMPK activation and the role of AMPK in the regulation of cellular energy balance. We summarize recent studies implicating AMPK activation in the regulation of neuronal survival and as a key player during ischemic stroke. We also suggest that AMPK activation may have dual functions in the regulation of neuronal survival: AMPK provides a protective effect during transient energy depletion as exemplified in a model of neuronal Ca2+ overloading, and this effect is partially mediated by the activation of neuronal glucose transporter 3. Prolonged AMPK activation, on the contrary, can lead to neuronal apoptosis via the transcriptional activation of the proapoptotic Bcl-2 family member, bim. Molecular switches that determine the protective versus cell death-inducing effects of AMPK activation are discussed.

    Original languageEnglish (US)
    Pages (from-to)1863-1876
    Number of pages14
    JournalAntioxidants and Redox Signaling
    Volume14
    Issue number10
    DOIs
    StatePublished - May 15 2011

    ASJC Scopus subject areas

    • Biochemistry
    • Physiology
    • Molecular Biology
    • Clinical Biochemistry
    • Cell Biology

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