Metabolism and function of N-acetylaspartate, N-acetylaspartylglutamate and related metabolites

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N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) are abundant metabolites in the nervous system of vertebrates. NAAG is formed by NAAG synthetases using NAA and glutamate. Since many years, NAA is used as a marker for neurodegeneration, however, its physiological role is largely unknown. Because a genetic defect in the NAA degradation causes a severe leukodystrophy, it has been hypothesized that NAA may serve as a carrier for acetyl groups used for myelin lipid synthesis in oligodendrocytes. NAAG may have neuroprotective functions. This project has two main topics. First, we will analyze the in vivo role of NAA in myelination and the role of NAAG in neuroprotection and synaptic plasticity. This will be examined using new transgenic mouse lines. Second, the enzymatic properties and protein interactions of NAA synthase and NAAG synthetases will be examined. In addition, we try to identify the NAAG transporter in synaptic vesicles.