Activity-based NIR specific fluorescent probe reveals the abnormal elevation of prolyl endopeptidase in hippocampus during Alzheimer's disease progression

被引：6

作者：

Li, Hao ^{[1
]}

Bian, Kun-Jie ^{[1
,2
]}

Wang, Xiu-Yang ^{[1
]}

Li, Xiao-Dong ^{[1
]}

Song, Pei-Fang ^{[1
]}

Yu, Chun-Yang ^{[3
]}

Ge, Guang-Bo ^{[1
]}

Qian, Xing-Kai ^{[2
,4
]}

Zou, Li-Wei ^{[1
,3
]}

Zhou, Yong-Feng ^{[3
]}

Yang, Ling ^{[1
,5
]}

机构：

[1] Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai 201203, Peoples R China

[2] Guizhou Med Univ, Translat Med Res Ctr, Guiyang 550025, Guizhou, Peoples R China

[3] Shanghai Jiao Tong Univ, Frontiers Sci Ctr Transformat Mol, Sch Chem & Chem Engn, Shanghai 200240, Peoples R China

[4] Guizhou Med Univ, Affiliated Hosp, Dept Cardiac Surg, Guiyang 550001, Guizhou, Peoples R China

[5] Zunyi Med Univ, Sch Pharm, Zunyi 563006, Peoples R China

来源：

SENSORS AND ACTUATORS B-CHEMICAL | 2024年 / 417卷

关键词：

Prolyl endopeptidase; NIR fluorescent probe; Brain imaging; Alzheimer's disease; PARKINSONS-DISEASE; PROGRAM PACKAGE; OLIGOPEPTIDASE; PROTEIN; EXPRESSION; FLUID; BETA; BDF;

D O I：

10.1016/j.snb.2024.136071

中图分类号：

O65 [分析化学];

学科分类号：

070302 ; 081704 ;

摘要：

Although prolyl endopeptidase (PREP) has become one of the important proteins to investigate the pathogenesis of Alzheimer's Disease (AD), the activity of PREP in the brain of AD patients is still controversial. This study aims to construct a novel enzyme-activated near-infrared (NIR) fluorescence probe for in-situ detection and imaging of PREP in brain, as well as to reveal the relationship between the activity variation of PREP and the development of AD. For these purposes, based on PREP's unique endopeptidase activity catalyzing prolyl-bond hydrolysis and cleavage, four probes deriving from a good NIR fluorophore (ACM) were designed and synthesized. Observations indicated that the Z-GP-ACM exhibited superior selectivity and sensitivity in detecting PREP. In addition, molecular thermodynamic/kinetic calculations and enzymatic kinetics studies also showed that Z-GP-ACM was an excellent substrate for PREP. Subsequent experiments demonstrated that Z-GP-ACM can be used to measure and image endogenous PREP in living cells and mouse brain. We also revealed for the first time that PREP activity was abnormally increased in hippocampus of AD mice during the disease progression. All these results highlighted that Z-GP-ACM could be a promising tool for exploring the biological functions of endogenous PREP in living systems.

引用

页数：11

共 52 条

[1] Glycogen synthase kinase-3 (GSK3): Regulation, actions, and diseases [J].