AMP-Activated Protein Kinase (AMPK) and Energy-Sensing in the Brain

Abstract

5'-adenosine monophosphate-activated protein kinase (AMPK) is an evolutionarily conserved cellular and organismal energy integrator that responds to numerous stimuli with the overall intention to facilitate energy conservation and enhance energy balance while also affecting cellular survival and behaviors. AMPK has been appreciated for many years to function in peripheral organs that contribute to the generation or disposition of cellular energy, while its role in the brain has been only recently elucidated. While acknowledged to respond to organismal energy balance, we now recognize that energy balance within neurons also affects the brain's response to these peripheral signals. In this review, we discuss AMPK's regulation and its ever-expanding role as a neuronal energy integrator at both the cellular and systems levels.

Keywords: 5'-adenosine monophosphate-activated kinase; AMPK; energy balance; feeding behavior; neuronal metabolism; stroke.

Fig. 1

Regulation of AMPK activation. AMPK is activated under conditions of energy-deficit by either physiological or pathophysiological signals. Signals that increase cellular AMP or ADP levels activate AMPK through LKB1, whereas those that raise intracellular Ca²⁺ activate AMPK through CaMKKβ. In contrast signals of energy-surplus inhibit AMPK activation and promote deactivation. Activated AMPK phosphorylates numerous targets to promote catabolic processes and inhibit anabolic cellular processes.