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Glutamine Synthetase: Role in Neurological Disorders

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The Glutamate/GABA-Glutamine Cycle

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 13))

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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Acknowledgements

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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Authors and Affiliations

  1. Laboratory of Neuropathology, Veterans Affairs Medical Center, Miami, FL, USA

    Arumugam R. Jayakumar & Michael D. Norenberg

  2. Departments of Pathology, University of Miami School of Medicine, 016960, Miami, FL, 33101, USA

    Michael D. Norenberg

  3. Departments of Biochemistry & Molecular Biology, University of Miami School of Medicine, Miami, FL, USA

    Michael D. Norenberg

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  1. Arumugam R. Jayakumar
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Correspondence to Michael D. Norenberg .

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  1. Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Arne Schousboe

  2. Department of Neuroscience, Norwegian University of Science and Technology (NTNU), Trondheim, Norway

    Ursula Sonnewald

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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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