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通过双光子成像观察单胺氧化酶活性与小鼠阿尔茨海默病进展的密切相关性

Close Correlation of Monoamine Oxidase Activity with Progress of Alzheimer's Disease in Mice, Observed by Two-Photon Imaging.

作者信息

Kim Dokyoung, Baik Sung Hoon, Kang Seokjo, Cho Seo Won, Bae Juryang, Cha Moon-Yong, Sailor Michael J, Mook-Jung Inhee, Ahn Kyo Han

机构信息

Department of Chemistry, Pohang University of Science and Technology (POSTECH), 77 Cheongam-Ro, Nam-Gu, Pohang, Gyungbuk 37673, Republic of Korea; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, United States.

Department of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University , 103 Daehak-Ro, Jongro-Gu, Seoul 110-799, Republic of Korea.

出版信息

ACS Cent Sci. 2016 Dec 28;2(12):967-975. doi: 10.1021/acscentsci.6b00309. Epub 2016 Dec 7.

Abstract

Monoamine oxidases (MAOs) play an important role in Alzheimer's disease (AD) pathology. We report comonitoring of MAO activity and amyloid-β (Aβ) plaques dependent on the aging of live mice with AD, using a two-photon fluorescence probe. The probe under the catalytic action of MAO produces a dipolar fluorophore that senses Aβ plaques, a general AD biomarker, enabling us to comonitor the enzyme activity and the progress of AD indicated by Aβ plaques. The results show that the progress of AD has a close correlation with MAO activity, which can be categorized into three stages: slow initiation stage up to three months, an aggressive stage, and a saturation stage from nine months. Histological analysis also reveals elevation of MAO activity around Aβ plaques in aged mice. The close correlation between the MAO activity and AD progress observed by monitoring for the first time prompts us to investigate the enzyme as a potential biomarker of AD.

摘要

单胺氧化酶(MAO)在阿尔茨海默病(AD)病理过程中发挥着重要作用。我们报告了使用双光子荧光探针,对患有AD的活体小鼠衰老过程中MAO活性和淀粉样β蛋白(Aβ)斑块进行共同监测的情况。该探针在MAO的催化作用下产生一种偶极荧光团,可检测作为AD通用生物标志物的Aβ斑块,从而使我们能够共同监测酶活性以及由Aβ斑块所指示的AD进展情况。结果表明,AD的进展与MAO活性密切相关,可分为三个阶段:长达三个月的缓慢起始阶段、一个侵袭性阶段以及从九个月开始的饱和阶段。组织学分析还揭示了老年小鼠Aβ斑块周围MAO活性升高。首次通过监测观察到的MAO活性与AD进展之间的密切相关性促使我们将该酶作为AD的潜在生物标志物进行研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d63/5200925/d108b69a8376/oc-2016-00309q_0001.jpg

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