| Roles of glutamine synthetase inhibition in epilepsy. | |
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MedLine Citation:
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PMID: 22488332 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Glutamine synthetase (GS, E.C. 6.3.1.2) 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. |
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Authors:
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Tore Eid; Kevin Behar; Ronnie Dhaher; Argyle V Bumanglag; Tih-Shih W Lee |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review Date: 2012-04-10 |
Journal Detail:
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Title: Neurochemical research Volume: 37 ISSN: 1573-6903 ISO Abbreviation: Neurochem. Res. Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-05 Completed Date: 2013-04-23 Revised Date: 2013-05-06 |
Medline Journal Info:
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Nlm Unique ID: 7613461 Medline TA: Neurochem Res Country: United States |
Other Details:
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Languages: eng Pagination: 2339-50 Citation Subset: IM |
Affiliation:
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Department of Laboratory Medicine, Yale University School of Medicine, 330 Cedar Street, P.O. Box 208035, New Haven, CT 06520-8035, USA. Tore.eid@yale.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Ammonia
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metabolism Animals Epilepsy / enzymology*, metabolism Glutamate-Ammonia Ligase / antagonists & inhibitors* Glutamic Acid / metabolism Glutamine / metabolism Humans gamma-Aminobutyric Acid / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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K08 NS058674/NS/NINDS NIH HHS; K08 NS058674/NS/NINDS NIH HHS; R01 MH095104/MH/NIMH NIH HHS; R01 NS070824/NS/NINDS NIH HHS; R01 NS070824/NS/NINDS NIH HHS; UL1 RR024139/RR/NCRR NIH HHS; UL1 RR024139/RR/NCRR NIH HHS; UL1 TR000142/TR/NCATS NIH HHS |
| Chemical | |
Reg. No./Substance:
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56-12-2/gamma-Aminobutyric Acid; 56-85-9/Glutamine; 56-86-0/Glutamic Acid; 7664-41-7/Ammonia; EC 6.3.1.2/Glutamate-Ammonia Ligase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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