A growing body of evidence emphasizes that hypometabolism taking place in astrocytes may compromise their physiological neuro-supportive role and activate a set of pathophysiological pathways contributing to the progression of neurodegenerative diseases, including Alzheimer disease (AD) [1]. Here, we explored the potential role of astrocytes in driving a cascade of detrimental effects in the neighboring neurons and investigated a possible approach to limit the injury in both cell types [2]. To this aim, primary rat cortical astrocytes were exposed to glyceraldehyde (GA) to induce a metabolic stress [3]. Cellular viability, ATP production, inflammatory state and oxidative stress were assessed with and without glutamate, used as an alternative metabolic substrate. We observed that GA caused a concentration-dependent damage, a reduction in ATP synthesis, the activation of the NF-kB pathway, an increase in TNFα release, the upregulation of glutamate transporters and a rise in reactive oxygen species (ROS) production, effects that were all mitigated by glutamate. Co-culturing injured astrocytes with neurons resulted in a significant neuronal viability reduction, along with the increase in AD markers levels and ROS overproduction. When glutamate-rescued astrocytes were co-cultured with neurons, we observed an improvement in neuronal viability and a decrease in AD marker and ROS levels.This research suggests that compromised astrocytic energetics may affect the neighboring neurons, triggering a cascade of events leading to AD, and underscores the importance of exploring astrocyte-targeted therapies for potential neuroprotective interventions. Nat Rev Neurosci 2019 Mar;20(3):148-160.Front Neurol. 2021; 12: 619626.Cells. 2021 Aug 17;10(8):2109.