Peripheral and Central Glutamate Dyshomeostasis in Neurodegenerative Disorders

Curr Neuropharmacol. 2021;19(7):1069-1089. doi: 10.2174/1570159X18666201015161919.


Glutamate's role as the major excitatory neurotransmitter of the mammalian central nervous system requires that its brain concentrations be kept tightly-controlled. However, in hepatic encephalopathy resulting from liver dysfunction; disruption of central neurotransmission and elevation of brain glutamate levels have been observed. These had been associated with certain neurological changes. While neurological changes resulting from hepatic encephalopathy are believed to be transient, the discovery of alterations in liver enzymes in Alzheimer's disease and the role of glutamate and glutamate homeostasis in hepatic encephalopathy have piqued interests in the possible role of glutamate, and glutamate homeostasis in neurodegenerative diseases. Here, we discuss the evidence in support of the involvement of peripheral/central glutamate homeostasis in the development of neurodegenerative disorders, as well as, the implications of such interactions in the development of new therapies for neurodegenerative disorders.

Keywords: Gut-liver brain axis; cystine-glutamate antiporter.; glutamate receptors; sodium-dependent transporter.

MeSH terms

  • Alzheimer Disease*
  • Animals
  • Brain
  • Glutamic Acid
  • Humans
  • Neurodegenerative Diseases*
  • Synaptic Transmission


  • Glutamic Acid