单胺氧化酶A/B亚型的活性检测在神经系统疾病诊疗中的应用  

Application of MAO-A/B subtype activity detection in diagnosis and treatment of neurological diseases

作　　者：王莉敏 方斌 方海啸 柏桦 李林 WANG Limin;FANG Bin;FANG Haixiao;BAI Hua;LI Lin(Shaanxi Institute of Flexible Electronics(SIFE),Frontiers Science Center for Flexible Electronics(FSCFE),Shaanxi Institute of Biomedical Materials and Engineering(SIBME),Northwestern Polytechnical University(NPU),Xi'an 710072,Shaanxi,China;Key Laboratory of Flexible Electronics(KLOFE)&Institute of Advanced Materials(IAM),Nanjing Tech University(NanjingTech),Nanjing 211816,Jiangsu,China)

机构地区：[1]西北工业大学柔性电子研究院&柔性电子前沿科学中心&生物医学材料与工程研究院,陕西西安710072 [2]南京工业大学先进材料研究院,江苏南京211816

出　　处：《中国临床药理学与治疗学》2020年第9期1052-1058,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金面上项目(81672508)(22077101);陕西省自然科学基础研究计划资助项目(2019JM-016);西北工业大学研究生创意创新种子基金项目(CX2020289)。

摘　　要：分布于线粒体外膜上的单胺氧化酶(monoamine oxidase,MAOs)表达异常会引起神经递质传递功能紊乱,与精神性和神经退行性疾病有着密切联系。因此,对于MAOs(MAO-A/B)活性的特异性检测和调控将有助于神经系统相关疾病的诊断和治疗;利用特异性强、灵敏度高的荧光检测/成像技术区分MAO-A/B两种亚型具有重要的生物学意义。本课题组基于“空间构型转换”的概念,设计特异性荧光“Switch-ON”行为的双光子小分子荧光探针U1和F1,结合双光子荧光显微成像技术在细胞和组织层面上分别实现对内源性MAO-B和MAO-A的特异性活性检测,旨在为进一步理解MAOs的生理作用,开发MAOs抑制剂创新药物及神经系统疾病的诊疗提供帮助。The abnormal expression of monoamine oxidases(MAOs),which distributed on the outer mitochondrial membrane can cause the dysfunction of neurotransmitter delivery and related to mental and neurodegenerative diseases.Therefore,the specific detection of MAOs(MAO-A/B)and the regulation of their activities will contribute to the diagnosis and treatment of neurological diseases.In order to distinguish the two subtypes of MAO-A/B,fluorescence detection and imaging techniques with highly specific and sensitive properties have important biological relevance.Herein,our research group based on the concept of"spatial configuration conversion"have designed the two-photon small molecule fluorogenic probes of U1 and F1,which capable of specific fluorescence"Switch-ON"behaviour,and combined with two-photon fluorescence microscopic imaging technology to realize the activity detection of endogenous MAO-B/A in cells and tissues.It is hoped that this works will benefit the understanding of physiological function about MAOs and developing innovative inhibitors,as well as diagnosing and treating in neurological diseases.

关 键 词：神经系统疾病 单胺氧化酶 荧光探针 活性检测 

分 类 号：R-331[医药卫生] Q5-33[生物学—生物化学]