The dual face of glutamate: from a neurotoxin to a potential survival factor—metabolic implications in health and disease

  • Simona MagiEmail author
  • Silvia Piccirillo
  • Salvatore Amoroso


Glutamate is the major excitatory neurotransmitter in the central nervous system. Beyond this function, glutamate also plays a key role in intermediary metabolism in all organs and tissues, linking carbohydrate and amino acid metabolism via the tricarboxylic acid cycle. Under both physiological and pathological conditions, we have recently found that the ability of glutamate to fuel cell metabolism selectively relies on the activity of two main transporters: the sodium–calcium exchanger (NCX) and the sodium-dependent excitatory amino-acid transporters (EAATs). In ischemic settings, when glutamate is administered at the onset of the reoxygenation phase, the coordinate activity of EAAT and NCX allows glutamate to improve cell viability by stimulating ATP production. So far, this phenomenon has been observed in both cardiac and neuronal models. In this review, we focus on the most recent findings exploring the unusual activity of glutamate as a potential survival factor in different settings.


Amino-acid transporters ATP Cell viability Ischemia/reperfusion Sodium–calcium exchanger 



Alzheimer’s disease


Amyotrophic lateral sclerosis


Aspartate/glutamate carriers


α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid


DL-Threo-β-benzyloxyaspartic acid


Excitatory amino acid carrier 1


Excitatory amino-acid transporters




Glutamate–aspartate transporter


Glutamate transporter 1


Metabotropic glutamate receptors


Sodium–calcium exchanger




2-[[4-[(4-Nitrophenyl)methoxy]phenyl]methyl]-4-thiazolidinecarboxylic acid ethyl ester



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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Biomedical Sciences and Public Health, School of MedicineUniversity “Politecnica delle Marche”AnconaItaly

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