The unsolved puzzle of neuropathogenesis in glutaric aciduria type I.

Details

Ressource 1Request a copy Sous embargo indéterminé.
State: Public
Version: Final published version
Serval ID
serval:BIB_CF30CCF60ADD
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
The unsolved puzzle of neuropathogenesis in glutaric aciduria type I.
Journal
Molecular Genetics and Metabolism
Author(s)
Jafari P., Braissant O., Bonafé L., Ballhausen D.
ISSN
1096-7206 (Electronic)
ISSN-L
1096-7192
Publication state
Published
Issued date
2011
Peer-reviewed
Oui
Volume
104
Number
4
Pages
425-437
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
Glutaric aciduria type I (GA-I) is a cerebral organic aciduria caused by deficiency of glutaryl-Co-A dehydrogenase (GCDH). GCDH deficiency leads to accumulation of glutaric acid (GA) and 3-hydroxyglutaric acid (3-OHGA), two metabolites that are believed to be neurotoxic, in brain and body fluids. The disorder usually becomes clinically manifest during a catabolic state (e.g. intercurrent illness) with an acute encephalopathic crisis that results in striatal necrosis and in a permanent dystonic-dyskinetic movement disorder. The results of numerous in vitro and in vivo studies have pointed to three main mechanisms involved in the metabolite-mediated neuronal damage: excitotoxicity, impairment of energy metabolism and oxidative stress. There is evidence that during a metabolic crisis GA and its metabolites are produced endogenously in the CNS and accumulate because of limiting transport mechanisms across the blood-brain barrier. Despite extensive experimental work, the relative contribution of the proposed pathogenic mechanisms remains unclear and specific therapeutic approaches have yet to be developed. Here, we review the experimental evidence and try to delineate possible pathogenetic models and approaches for future studies.
Pubmed
Web of science
Create date
01/12/2011 17:37
Last modification date
20/08/2019 16:49
Usage data