Function of the master energy regulator adenosine monophosphate-activated protein kinase in stroke

Adenosine monophosphate-activated protein kinase (AMPK) is an evolutionarily conserved signaling molecule that is emerging as one of the most important energy sensors in the body. AMPK monitors cellular energy status and is activated via phosphorylation when energy stores are low. This allows for maintenance of energy homeostasis by promoting catabolic pathways for ATP production and limiting processes that consume ATP. Growing number of stimuli have been shown to activate AMPK, and AMPK has been implicated in many diverse biological processes, including cell polarity, autophagy, and senescence. The effect of AMPK activation and its biological functions are extremely diverse and depend on both the overall energy "milieu" and the location and duration of activation. AMPK has tissue- and isoform-specific functions in the brain vs. periphery. These functions and the pathways activated also appear to differ by cell location (hypothalamus vs. cortex), cell type (astrocyte vs. neuron), and duration of exposure. Short bursts of AMPK activation have been found to be involved in ischemic preconditioning and neuronal survival; however, prolonged AMPK activity during ischemia leads to neuronal cell death. AMPK may also underlie some of the beneficial effects of hypothermia, a potential therapy for ischemic brain injury. This review discusses the role of AMPK in ischemic stroke, a condition of severe energy depletion.