Activation of the AMPK Signaling and Brain Function: A Friend or Foe?

AMP-activated protein kinase (AMPK) is a central regulator of cellular energy balance, and its activation presents a therapeutic strategy for various metabolic diseases and neuronal disorders. Yet its effects on brain function remain unclear. This review evaluates evidence from animal and human studies examining AMPK activation through pharmacological agents (synthetic or natural compounds) and exercise. The effects of AMPK activation on synaptic and cognitive function seem highly context-dependent. Peripheral or acute AMPK activation often improves cognition, whereas chronic or central nervous system (CNS) activation can impair synaptic plasticity and memory. Collectively, current studies underscore the need for rigorous research distinguishing peripheral versus central AMPK activation, clarifying isoform-specific signaling, and examining effects in healthy human populations.