Abstract
Summary: Although the precise mechanisms underlying the CNS degeneration of patients with glutaryl-CoA dehydrogenase (GCDH) deficiency are still the subject of intense debate, many studies have highlighted that excitotoxicity plays a fundamental role in the neuropathology of this disease, particularly involving the N-methyl-D-aspartate receptor subtype of ionotropic glutamate receptors. Modulation of the glutamatergic system by these compounds involves an inhibition of glutamate uptake into synaptosomes and synaptic vesicles, and a decrease in glutamate binding. Furthermore, glutaric and 3-hydroxyglutaric acids inhibit glutamate decarboxylase, the key enzyme of GABA synthesis, and striatal GABAergic medium-spiny neurons are highly vulnerable to 3-hydroxyglutaric acid-induced neurotoxicity. In conclusion, glutaric acid and 3-hydroxyglutaric acid induce an imbalance in glutamatergic and GABAergic neurotransmission.
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Wajner, M., KÖlker, S., Souza, D.O. et al. Modulation of glutamatergic and GABAergic neurotransmission in glutaryl-CoA dehydrogenase deficiency. J Inherit Metab Dis 27, 825–828 (2004). https://doi.org/10.1023/B:BOLI.0000045765.37043.fb
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DOI: https://doi.org/10.1023/B:BOLI.0000045765.37043.fb