Current concepts in the pathogenesis of urea cycle disorders.

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State: Public
Version: author
Serval ID
serval:BIB_7D1C82D03242
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Current concepts in the pathogenesis of urea cycle disorders.
Journal
Molecular Genetics and Metabolism
Author(s)
Braissant Olivier
ISSN
1096-7206[electronic], 1096-7192[linking]
Publication state
Published
Issued date
2010
Peer-reviewed
Oui
Volume
100
Number
Suppl 1
Pages
S3-S12
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Review
Publication Status: ppublish
Abstract
The common feature of urea cycle diseases (UCD) is a defect in ammonium elimination in liver, leading to hyperammonemia. This excess of circulating ammonium eventually reaches the central nervous system, where the main toxic effects of ammonium occur. These are reversible or irreversible, depending on the age of onset as well as the duration and the level of ammonium exposure. The brain is much more susceptible to the deleterious effects of ammonium during development than in adulthood, and surviving UCD patients may develop cortical and basal ganglia hypodensities, cortical atrophy, white matter atrophy or hypomyelination and ventricular dilatation. While for a long time, the mechanisms leading to these irreversible effects of ammonium exposure on the brain remained poorly understood, these last few years have brought new data showing in particular that ammonium exposure alters several amino acid pathways and neurotransmitter systems, cerebral energy, nitric oxide synthesis, axonal and dendritic growth, signal transduction pathways, as well as K(+) and water channels. All these effects of ammonium on CNS may eventually lead to energy deficit, oxidative stress and cell death. Recent work also proposed neuroprotective strategies, such as the use of NMDA receptor antagonists, nitric oxide inhibitors, creatine and acetyl-l-carnitine, to counteract the toxic effects of ammonium. Better understanding the pathophysiology of ammonium toxicity to the brain under UCD will allow the development of new strategies for neuroprotection.
Keywords
Animals, Central Nervous System/drug effects, Central Nervous System/pathology, Disease Models, Animal, Humans, Hyperammonemia/complications, Quaternary Ammonium Compounds/toxicity, Urea Cycle Disorders, Inborn/etiology
Pubmed
Web of science
Create date
26/02/2010 8:34
Last modification date
20/08/2019 14:38
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