Roles of glutamine synthetase inhibition in epilepsy.


Journal Article (Review)

Glutamine synthetase (GS, E.C. is a ubiquitous and highly compartmentalized enzyme that is critically involved in several metabolic pathways in the brain, including the glutamine-glutamate-GABA cycle and detoxification of ammonia. GS is normally localized to the cytoplasm of most astrocytes, with elevated concentrations of the enzyme being present in perivascular endfeet and in processes close to excitatory synapses. Interestingly, an increasing number of studies have indicated that the expression, distribution, or activity of brain GS is altered in several brain disorders, including Alzheimer's disease, schizophrenia, depression, suicidality, and mesial temporal lobe epilepsy (MTLE). Although the metabolic and functional sequelae of brain GS perturbations are not fully understood, it is likely that a deficiency in brain GS will have a significant biological impact due to the critical metabolic role of the enzyme. Furthermore, it is possible that restoration of GS in astrocytes lacking the enzyme could constitute a novel and highly specific therapy for these disorders. The goals of this review are to summarize key features of mammalian GS under normal conditions, and discuss the consequences of GS deficiency in brain disorders, specifically MTLE.

Full Text

Cited Authors

  • Eid, T; Behar, K; Dhaher, R; Bumanglag, AV; Lee, T-SW

Published Date

  • November 2012

Published In

Volume / Issue

  • 37 / 11

Start / End Page

  • 2339 - 2350

PubMed ID

  • 22488332

Pubmed Central ID

  • 22488332

Electronic International Standard Serial Number (EISSN)

  • 1573-6903

International Standard Serial Number (ISSN)

  • 0364-3190

Digital Object Identifier (DOI)

  • 10.1007/s11064-012-0766-5


  • eng