N-乙酰天冬氨酸在中枢神经系统中的研究进展

Progress in research of N-acetylaspartate in central nervous system

N-乙酰天冬氨酸(N-acetylaspartate,NAA)是一种在大脑中大量存在的代谢物。NAA作为一种反映神经系统功能情况的重要标志物,广泛应用于核磁共振波谱(proton magnetic resonance spectroscopy,1H MRS)技术对脑内代谢产物的分析中。NAA在神经元内的线粒体内合成,进入少突胶质细胞内代谢,或在神经元内合成N-乙酰天冬氨酰谷氨酸(N-acetylaspartylglutamate,NAAG),经星形胶质细胞摄取分解。研究发现,NAA与多种中枢神经系统疾病相关,包括Canavan疾病、多发性硬化以及抑郁症、精神分裂症等精神疾病,因此,NAA可能作为这些疾病的生物标志物,其相关酶可能作为治疗靶点进行药物筛选。本文将从NAA分子机制研究入手,介绍NAA在脑内的生成、代谢与转运过程,阐述其可能发挥的生理作用,并对NAA在中枢神经系统疾病中的相关研究进展进行综述,探讨NAA在疾病的预测、诊断方面的前景,以及可能成为难治性疾病突破口的靶向治疗方式。

N-Acetylaspartate(NAA)is a highly abundant brain metabolite.Nowadays,as an important marker reflecting the function of nervous system,NAA is widely used in the results analysis of nuclear magnetic resonance spectroscopy(1 H MRS).NAA is synthesized in mitochondria of neurons and metabolized in oligodendrocytes.Additionally,NAA may be converted to the dipeptide N-acetylaspartylglutamate(NAAG),and catabolized into NAA and glutamate in astrocytes.NAA is related to a variety of central nervous system diseases,including Canavan disease,multiple sclerosis,depression,schizophrenia and other mental diseases.Therefore,NAA may be a biomarker of these diseases,and its related enzymes may be used as therapeutic targets for drug screening.Here,we combined the current research on the molecular mechanisms of NAA to reveal the process of NAA generation,metabolism and transport in the brain,explain the possible physiological effects of NAA and discuss its relationship with central nervous system diseases,explore the prospect of NAA in disease prediction and diagnosis,as well as the targeted treatment that may become the breakthrough of refractory diseases.