ReviewNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2010
Astrocyte glutamine synthetase: importance in hyperammonemic syndromes and potential target for therapy.
Review in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed, 201 citations in OpenAlex.
- Which of the branched-chain amino acids increases cerebral blood flow in hepatic encephalopathy? A double-blind randomized trial.NeuroImage. Clinical · 2018Trial
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- Review
- Post-meal loss of consciousness in an adult patient with carbamoyl phosphate synthetase 1 deficiency and two newly identified heterozygous variants: a case report.BMC neurology · 2026Article
- Serum amino acid levels are associated with brain hypometabolism in patients across the Alzheimer's disease continuum.IBRO neuroscience reports · 2026Article
- A Novel Gain-of-Function GLUL Variant Is Associated With Developmental and Epileptic Encephalopathy With Enlarged Perivascular Spaces.Human mutation · 2026Article
- Regeneration-Associated Factors in the Regulation of Adult and Post-Traumatic Neurogenesis in the Forebrain of Fish and Other Vertebrates.International journal of molecular sciences · 2025Review
- Effects ofiMetaOmics · 2025Article
- Oedematic-atrophic astrocytes in hepatic encephalopathy.Acta neuropathologica communications · 2025Article
- Glutamine Synthetase: Diverse Regulation and Functions of an Ancient Enzyme.Biochemistry · 2025Review
- Motor performance as a predictor of blood levels of ammonia and inflammatory biomarkers in patients with liver cirrhosis.PloS one · 2025Article
- D-glucaro-1,4-lactone alleviates acetaminophen-induced hepatotoxicity in mice via modulating gut microbiota and metabolites associated withFrontiers in pharmacology · 2025Article
- Case Report: Management of intracranial hypertension in acute-on-chronic liver failure: a case of fulminant cerebral edema and acute-onset severe hyperammonemia in a patient with cirrhosis.Frontiers in gastroenterology (Lausanne, Switzerland) · 2025Article
- Hepatic encephalopathy treatment after transjugular intrahepatic portosystemic shunt: a new perspective on the gut microbiota.Frontiers in medicine · 2025Review
- Modulation of brain energy metabolism in hepatic encephalopathy: impact of glucose metabolic dysfunction.Metabolic brain disease · 2024Review
- Implication of Hypotension in the Pathogenesis of Cognitive Impairment and Brain Injury in Chronic Liver Disease.Neurochemical research · 2024Review
- Clustered de novo start-loss variants in GLUL result in a developmental and epileptic encephalopathy via stabilization of glutamine synthetase.American journal of human genetics · 2024Article
- The Role of Astrocytic Mitochondria in the Pathogenesis of Brain Ischemia.Molecular neurobiology · 2024Review
- The role of glutamate and glutamine metabolism and related transporters in nerve cells.CNS neuroscience & therapeutics · 2024Review
- Astrocytes in human central nervous system diseases: a frontier for new therapies.Signal transduction and targeted therapy · 2023Review
43 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 4 institutions in 1 country.
Funding
Abstract
Many theories have been advanced to explain the encephalopathy associated with chronic liver disease and with the less common acute form. A major factor contributing to hepatic encephalopathy is hyperammonemia resulting from portacaval shunting and/or liver damage. However, an increasing number of causes of hyperammonemic encephalopathy have been discovered that present with the same clinical and laboratory features found in acute liver failure, but without liver failure. Here, we critically review the physiology, pathology, and biochemistry of ammonia (i.e., NH3 plus NH4+) and show how these elements interact to constitute a syndrome that clinicians refer to as hyperammonemic encephalopathy (i.e., acute liver failure, fulminant hepatic failure, chronic liver disease). Included will be a brief history of the status of ammonia and the centrality of the astrocyte in brain nitrogen metabolism. Ammonia is normally detoxified in the liver and extrahepatic tissues by conversion to urea and glutamine, respectively. In the brain, glutamine synthesis is largely confined to astrocytes, and it is generally accepted that in hyperammonemia excess glutamine compromises astrocyte morphology and function. Mechanisms postulated to account for this toxicity will be examined with emphasis on the osmotic effects of excess glutamine (the osmotic gliopathy theory). Because hyperammonemia causes osmotic stress and encephalopathy in patients with normal or abnormal liver function alike, the term "hyperammonemic encephalopathy" can be broadly applied to encephalopathy resulting from liver disease and from various other diseases that produce hyperammonemia. Finally, the possibility that a brain glutamine synthetase inhibitor may be of therapeutic benefit, especially in the acute form of liver disease, is discussed.
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