Functional insights from targeted imaging BACE1: the first near-infrared fluorescent probe for Alzheimer’s disease diagnosis
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Published:2022-12-09
Issue:1
Volume:26
Page:
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ISSN:2055-7124
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Container-title:Biomaterials Research
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language:en
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Short-container-title:Biomater Res
Author:
Bi Anyao,Wu Junyong,Huang Shuai,Li Yongjiang,Zheng Fan,Ding Jipeng,Dong Jie,Xiang Daxiong,Zeng Wenbin
Abstract
Abstract
Background
β-Secretase (BACE1) is the vital enzyme in the pathogenic processes of Alzheimer's disease (AD). However, the development of a powerful tool with sensitivity for BACE1 determination in vivo is a challenge.
Methods
A novel NIR fluorescent probe HBAE was synthetized from 2-hydroxy-3-methylbenzaldehyde and 2-amino-benzenethiol by 5 steps. The fluorescence mechanism in the ESIPT systems of HBAE probe was insighted with time-dependent density functional theory (TD-DFT) at the TDPBE0 level with the def2-TZVP approach. The corresponding docking between HBAE and BACE1 (PDB: 5I3Y) was performed through the ducking method by DOCK6.8. Then the BBB permeability of HBAE is verified by transwell orifice plate. 22-month-old male AD-model (5XFAD) mice and age-matched wild-type mice were employed to observe the brain kinetics by intravenous injection. Finally, Immunohistochemistry was performed on the AD brain section to reveal the levels of BACE1 in hippocampus and cortex areas and other regions in AD mice through the brain tissue slices by HBAE.
Results
The NIR fluorescent probe HBAE was successfully applied in imaging BACE1 in AD model mice. The capability of HBAE in reflecting different level of BACE1 was performed by the specific imaging of the hippocampus region.
Conclusions
We reported the first ESIPT near-infrared fluorescence probe HBAE for monitoring endogenous BACE1 in the AD live model mice, thus offering a versatile chemical tool for visualizing in the pathological processes of AD live brains. Remarkably, high resolution images showed the localization of red fluorescence stains in hippocampus of the AD brain. This study provides a promising way for functional insights from protein BACE1 in vivo.
Funder
National Natural Science Foundation of China
Science and Technology Foundation of Hunan Province
the Innovation Fund for Postgraduate Students of Central South University
the Fundamental Research Funds for the Central Universities of Central South University
Publisher
Springer Science and Business Media LLC
Subject
Biomedical Engineering,Biomaterials,Medicine (miscellaneous),Ceramics and Composites
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