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NAAG synthetase deficiency has only low influence on pathogenesis in a Canavan disease mouse model.
J Inherit Metab Dis
March 2024
Institute of Biochemistry and Molecular Biology, Medical Faculty, University of Bonn, Bonn, Germany.
Canavan disease (CD) is a leukodystrophy caused by mutations in the N-acetylaspartate (NAA) hydrolase aspartoacylase (ASPA). Inability to degrade NAA and its accumulation in the brain results in spongiform myelin degeneration. NAA is mainly synthesized by neurons, where it is also a precursor of the neuropeptide N-acetylaspartylglutamate (NAAG).
View Article and Find Full Text PDFAn enzymatic fluorimetric assay for determination of N-acetylaspartate.
Anal Biochem
April 2023
Institute of Biochemistry and Molecular Biology, Medical Faculty, University of Bonn, Nussallee 11, 53115, Bonn, Germany. Electronic address:
N-acetylaspartate (NAA) is an abundant metabolite in the mammalian brain and a precursor of the neuropeptide N-acetylaspartylglutamate (NAAG). The physiological role of NAA is not fully understood and requires further studies. We here describe the development of a coupled enzymatic fluorimetric assay for the determination of NAA in biological samples.
View Article and Find Full Text PDFDendrimer-2PMPA selectively blocks upregulated microglial GCPII activity and improves cognition in a mouse model of multiple sclerosis.
Nanotheranostics
March 2022
Johns Hopkins Drug Discovery, Johns Hopkins University, Baltimore, MD, USA.
Cognitive impairment is a common aspect of multiple sclerosis (MS) for which there are no treatments. Reduced brain -acetylaspartylglutamate (NAAG) levels are linked to impaired cognition in various neurological diseases, including MS. NAAG levels are regulated by glutamate carboxypeptidase II (GCPII), which hydrolyzes the neuropeptide to -acetyl-aspartate and glutamate.
View Article and Find Full Text PDFMice deficient in the NAAG synthetase II gene Rimkla are impaired in a novel object recognition task.
J Neurochem
June 2021
Institute of Biochemistry and Molecular Biology, Medical Faculty, University of Bonn, Bonn, Germany.
N-acetylaspartylglutamate (NAAG) is an abundant neuropeptide in the mammalian nervous system, synthesized by two related NAAG synthetases I and II (NAAGS-I and -II) encoded by the genes Rimklb and Rimkla, respectively. NAAG plays a role in cognition and memory, according to studies using inhibitors of the NAAG hydrolase glutamate carboxypeptidase II that increase NAAG concentration. To examine consequences of reduced NAAG concentration, Rimkla-deficient (Rimkla ) mice were generated.
View Article and Find Full Text PDFEvidence of NAAG-family tripeptide NAAG in the Drosophila nervous system.
J Neurochem
January 2021
Biology Department, Grinnell College, Grinnell, IA, USA.
N-acetylaspartylglutamate (NAAG) is a common neurotransmitter in the mammalian nervous system; however, it has never been reported in the nervous system of the fruit fly, Drosophila melanogaster. Using antiserum against NAAG, we localized NAAG-like immunoreactivity to neurons in the ventral nerve cord and to type Is glutamatergic nerve terminals in larval neuromuscular junctions. Using liquid chromatography tandem mass spectrometry (LC-MS), we failed to find NAAG but found the related peptide N-acetylaspartylglutamylglutamate (NAAG ) in Drosophila CNS and body wall tissue.
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