Abstract
Glutamine synthetase (GS) is an ATP-dependent enzyme found in most species that synthesizes glutamine from glutamate and ammonia. In brain, GS is exclusively located in astrocytes where it serves to maintain the glutamate–glutamine cycle, as well as nitrogen metabolism. Changes in the activity of GS, as well as its gene expression, along with excitotoxicity, have been identified in a number of neurological conditions. The literature describing alterations in the activation and gene expression of GS, as well as its involvement in different neurological disorders, however, is incomplete. This review summarizes changes in GS gene expression/activity and its potential contribution to the pathogenesis of several neurological disorders, including hepatic encephalopathy, ischemia, epilepsy, Alzheimer’s disease, amyotrophic lateral sclerosis, traumatic brain injury, Parkinson’s disease, and astroglial neoplasms. This review also explores the possibility of targeting GS in the therapy of these conditions.
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Abbreviations
- AD:
-
Alzheimer’s disease
- ALS:
-
Amyotrophic lateral sclerosis
- Aβ:
-
Beta amyloid
- COX-2:
-
Cyclooxygenase-2
- EAAT:
-
Excitatory amino acid transporter
- GABA:
-
γ-aminobutyric acid
- GBM:
-
Glioblastoma multiforme
- GFAP:
-
Glial fibrillary acidic protein
- GLAST:
-
Glutamate-aspartate transporter
- GLT-1:
-
Glutamate transporter-1
- GS:
-
Glutamine synthetase
- HD:
-
Huntington’s disease
- HE:
-
Hepatic encephalopathy
- iNOS:
-
Inducible nitric oxide synthase
- MSO:
-
Methionine sulfoximine
- NMDA:
-
N-methyl-d-aspartate
- PCA:
-
Portacaval anastomosis
- TBI:
-
Traumatic brain injury
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This work was supported by a Merit Review from the US Department of Veterans Affairs and by a National Institutes of Health grant DK063311.
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Jayakumar, A.R., Norenberg, M.D. (2016). Glutamine Synthetase: Role in Neurological Disorders. In: Schousboe, A., Sonnewald, U. (eds) The Glutamate/GABA-Glutamine Cycle. Advances in Neurobiology, vol 13. Springer, Cham. https://doi.org/10.1007/978-3-319-45096-4_13
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