Perturbations in brain cell metabolism are consistently interwoven with neurodegenerative disorders like Alzheimer's disease (AD)(1). In particular, dysfunctions of mitochondrial bioenergetics incite severity of AD pathology (2), whereas proof-of-concept evidence indicates that glutamate can feed mitochondrial ATP synthesis, thereby preventing deadly derangements in Ca2+ and redox homeostasis in different neurodegenerative models (3;4).In this work, we tested a pharmacological approach to stimulate the glutamate dehydrogenase (GDH) function with the allosteric activator 2-Aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) and verify whether an increased anaplerotic GDH activity sustains mitochondrial ATP synthesis and cell survival in an in vitro model of AD. In particular, we used the neuron-like differentiated SH-SY5Y cells, exposed for 24 h to glyceraldehyde (GA) 1mM, a glycolysis inhibitor, to disrupt cell glucose metabolism and induce an AD-like phenotype (5).In our settings, the GA-induced fall in cellular ATP levels was significantly counteracted by 1 mM BCH used during the last three hours of GA exposure. This was also accompanied by a significant reduction of cell damage (as assessed by LDH and MTT assays) and of redox imbalance (as assessed by mitochondrial ROS production assay). Earlier or later applications of BCH (respectively during the last eight hours or during the last hour of GA exposure) elicited no protection against GA challenge.These findings emphasize the potential of modulating glutamate metabolism in order to mitigate the progression of AD-related neurodegeneration.1) Molecules. 2022;27(3):951.2) Int J Mol Sci. 2021;22(20):11185.3) Life Sci. 2021;285:119985.4) Biochem Pharmacol. 2022;203:1151635) Cells. 2021;10(8):2109