Glyceraldehyde-induced metabolic defects in cortical astrocytes: implication for Alzheimer's disease pathogenesis and therapy.

dyshomeostasis at both cytosolic and mitochondrial level (c) inflammation, measured as NF-κB activation, TNFα release, AGEs hyperproduction/RAGE hyperexpression and increase in S100β immunosignal, and, finally (d) autophagy impairment, characterized by the p62 and LC3II protein accumulation. By virtue of glutamate ability to stimulate cell metabolism, we examined the effect of the neurotransmitter supplementation on cell damage and those correlated mechanisms in the proposed AD model. Of interest, metabolic, inflammatory and autophagy defects were mitigated when astrocytes were exposed to glutamate as metabolic boosting substrate. The protective effect of glutamate was counteracted by the pharmacological inhibition of astrocytic glutamate transporters, thus highlighting the relevance of glutamate intracellular action. Collectively, these results highlight the importance of considering astrocyte-targeted therapies as potential strategy in AD.