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

N-乙酰天冬氨酸、N-乙酰天冬氨酰谷氨酸及相关代谢物的代谢和功能

• 批准号: 233613562
• 负责人: Privatdozent Dr. Matthias Eckhardt
• 金额: --
• 依托单位: Anatomisches Institut
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/233613562?language=en
• 关键词: Metabolism; function; acetylaspartate; acetylaspartylglutamate; related

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.

N-乙酰天冬氨酸（NAA）和N-乙酰谷氨酸（NAAG）是脊椎动物神经系统中含量丰富的代谢产物。NAAG由NAAG合成酶使用NAA和谷氨酸形成。多年来，NAA被用作神经变性的标志物，然而，其生理作用在很大程度上是未知的。由于NAA降解中的遗传缺陷导致严重的脑白质营养不良，因此假设NAA可以作为用于少突胶质细胞中髓鞘脂质合成的乙酰基的载体。NAAG可能具有神经保护作用。该项目有两个主要主题。首先，我们将分析在体内的作用，NAA的髓鞘形成和NAAG的神经保护和突触可塑性的作用。这将使用新的转基因小鼠品系进行检查。其次，将检查NAA合成酶和NAAG合成酶的酶性质和蛋白质相互作用。此外，我们试图确定突触囊泡中的NAAG转运蛋白。

项目成果

N-Acetylaspartate Synthase Deficiency Corrects the Myelin Phenotype in a Canavan Disease Mouse Model But Does Not Affect Survival Time

• DOI: 10.1523/jneurosci.1056-15.2015
• 发表时间: 2015-10-28
• 期刊: JOURNAL OF NEUROSCIENCE
• 影响因子: 5.3
• 作者: Maier, Helena;Wang-Eckhardt, Lihua;Eckhardt, Matthias
• 通讯作者: Eckhardt, Matthias