天冬氨酸酰基转移酶及其相关疾病的研究进展

Research progress of aspartoacylase and related disease

N-乙酰-L-天冬氨酸(NAA)是由神经元产生的天冬氨酸衍生物,是大脑中含量第二高的氨基酸/氨基酸衍生物,仅次于含量第1位的谷氨酸。NAA代谢通过影响水的运输、髓鞘合成、神经细胞能量代谢等方面进而影响神经系统功能,NAA增多或减少均会引起神经系统疾病。天冬氨酸酰基转移酶(ASPA)是将NAA分解为天冬氨酸和乙酸盐的酶,在维持NAA代谢平衡过程中发挥重要作用。ASPA突变可导致罕见病卡纳万病(CD),CD预后极差。此外,近些年关于甲基化ASPA基因在衰老预测模型中的报道逐渐增多,提示了ASPA在神经系统之外的作用。该文将对ASPA的生物学功能、ASPA突变所致CD的临床症状及治疗,以及甲基化ASPA基因在衰老中的作用进行综述。

N-acetyl-L-aspartic acid(NAA)is a derivative of aspartic acid produced by neurons and is the second most abundant amino acid/amino acid derivative in the brain,second only to the most abundant glutamic acid.NAA metabolism affects neurological system function through its impact on water transport,myelin synthesis,and neuron energy metabolism.Increase or decrease in NAA levels can lead to neurological diseases.Aspartoacylase(ASPA)is the enzyme responsible for catalyzing NAA into L-aspartate and acetate and plays an important role in maintaining NAA metabolism balance.ASPA mutations can cause the rare disease Canavan disease(CD),which has a very poor prognosis.In addition,in recent years,there have been increasing reports of the role of methylated ASPA gene in aging prediction models,indicating its role outside of the nervous system.This article reviews the biological functions of ASPA,the clinical symptoms and treatment of CD caused by ASPA mutations,and the role of methylated ASPA gene in aging.