The unsolved puzzle of neuropathogenesis in glutaric aciduria type I

Article ID	Journal	Published Year	Pages	File Type
10833799	Molecular Genetics and Metabolism	2011	13 Pages	PDF

Abstract

âº Despite numerous studies, neuropathogenesis of GA-I is only partially understood. âº Animal models and in vitro studies focusing on neurological damage are summarized. âº Intra-neuronal accumulation of GA seems to be an important pathomechanism. âº Excitotoxicity, impairment of energy metabolism and oxidative stress are involved. âº Intracerebral trapping of GA metabolites contribute to neuronal damage.

Keywords

RNS TCA GSH GPX BCB s.c.i.v.iNOS DCFH-DA i.p.NR2B DNQX AMPA TRAP APV IL-1β IFN-γ N-methyl-d-aspartate NMDA GCDH SDH glutaric aciduria type I NMG GA-I PDH CAT N-methyl-d-aspartate receptor subunit 2B PDC 2′,7′-dichlorofluorescein diacetate MAPK ROS 3-hydroxyglutaric acid α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid Quinolinic acid glutaric acid Oct excitotoxicity interferon-γ Interleukin-1β Cho Tar Chinese Hamster Ovary Oxidative stress Oat organic cation transporter organic anion transporter intra peritoneal intra venous CNS SOD Blood–brain barrier BBB inducible nitric oxide synthase Superoxide dismutase succinate dehydrogenase central nervous system Energy failure Vascular endothelial growth factor Vascular Endothelial Growth Factor (VEGF)Phosphocreatine not applicable Blood–cerebrospinal fluid barrier Neuropathogenesis Nitric oxide PCR mitogen-activated protein kinase pyruvate dehydrogenase tricarboxylic acid cycle Catalase creatine Creatine kinase Glu Glutathione glutathione peroxidase glutaryl-CoA dehydrogenase glutamate reactive nitrogen species Reactive oxygen species