title: Glutamine Synthetase: Role in Neurological Disorders.
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.
authors.affiliation: Laboratory of Neuropathology, Veterans Affairs Medical Center, Miami, FL, USA.
authors.forename: Arumugam R
authors.initials: AR
authors.lastname: Jayakumar
authors.affiliation: Laboratory of Neuropathology, Veterans Affairs Medical Center, Miami, FL, USA. mnorenbe@med.miami.edu.|Departments of Pathology, University of Miami School of Medicine, 016960, Miami, FL, 33101, USA. mnorenbe@med.miami.edu.|Departments of Biochemistry & Molecular Biology, University of Miami School of Medicine, Miami, FL, USA. mnorenbe@med.miami.edu.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Norenberg
mesh_terms: D000641:Ammonia / Q000378:metabolism; D001253:Astrocytes / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000096:biosynthesis; D006801:Humans; D009422:Nervous System Diseases / Q000201:enzymology* / Q000503:physiopathology / Q000628:therapy
chemical_list: D005973:Glutamine; D018698:Glutamic Acid; D000641:Ammonia; D005974:Glutamate-Ammonia Ligase
keywords: Ammonia; Astrocytes; Excitotoxicity; Glutamine; Glutamine synthetase; Neurological disorders; Neurotoxicity; Therapy