Astrocyte-mediated brain energy metabolism pathways (ANLS)

Astrocyte-mediated brain energy metabolism pathways represent the integrated metabolic processes, such as the Astrocyte-Neuron Lactate Shuttle (ANLS), that support neuronal function and survival [1, 3]. In these pathways, astrocytes take up glucose from the blood via GLUT1 and convert it into lactate through aerobic glycolysis, which is then shuttled to neurons via monocarboxylate transporters (MCT1, MCT4, and MCT2) to serve as an essential energy substrate for oxidative phosphorylation [1, 14]. This metabolic coupling is vital for synaptic plasticity, memory consolidation, and neuroprotection against oxidative stress [4, 10]. Dysregulation of these pathways is a hallmark of neurodegenerative diseases like Alzheimer's and acute injuries like ischemic stroke, where metabolic failure contributes to neuronal loss [1, 11]. Therapeutic strategies targeting these pathways, including small molecules like GP-119 and metabolic hormones like FGF21, aim to restore energy homeostasis and provide neuroprotective benefits [8, 17]. Additionally, GLP-1 receptor agonists and AMPK activators like metformin have been shown to modulate these astrocytic metabolic functions [5, 7]. However, modulating these complex systems requires careful consideration of potential side effects such as metabolic acidosis or off-target effects on peripheral glucose regulation [18, 30]. Overall, these pathways offer a promising frontier for treating conditions characterized by brain hypometabolism.

Other names

Astrocyte-Neuron Lactate ShuttleANLSAstrocytic metabolic supportNeuroenergetic couplingGlial-neuronal metabolic couplingAstrocyte-mediated metabolic pathways

Enhancement of astrocytic aerobic glycolysis, stimulation of lactate production and export via MCT1 and MCT4, promotion of neuronal lactate uptake via MCT2, and regulation of the glutamate-glutamine cycle to support neuronal ATP production [1, 8, 21].