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阿尔茨海默病的关键介质与成像靶点:通过单胺氧化酶B揭示反应性星形胶质细胞增生的作用

A Key Mediator and Imaging Target in Alzheimer's Disease: Unlocking the Role of Reactive Astrogliosis Through MAOB.

作者信息

Nam Min-Ho, Na Heesu, Justin Lee C, Yun Mijin

机构信息

Brain Science Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea.

Center for Cognition and Sociality, Institute for Basic Science, Daejeon, Republic of Korea.

出版信息

Nucl Med Mol Imaging. 2024 Jun;58(4):177-184. doi: 10.1007/s13139-023-00837-y. Epub 2024 Jan 15.

Abstract

Astrocytes primarily maintain physiological brain homeostasis. However, under various pathological conditions, they can undergo morphological, transcriptomic, and functional transformations, collectively referred to as reactive astrogliosis. Recent studies have accumulated lines of evidence that reactive astrogliosis plays a crucial role in the pathology of Alzheimer's disease (AD). In particular, monoamine oxidase B, a mitochondrial enzyme mainly expressed in astrocytes, significantly contributes to neuronal dysfunction and neurodegeneration in AD brains. Moreover, it has been reported that reactive astrogliosis precedes other pathological hallmarks such as amyloid-beta plaque deposition and tau tangle formation in AD. Due to the early onset and profound impact of reactive astrocytes on pathology, there have been extensive efforts in the past decade to visualize these cells in the brains of AD patients using positron emission tomography (PET) imaging. In this review, we summarize the recent studies regarding the essential pathological importance of reactive astrocytes in AD and their application as a target for PET imaging.

摘要

星形胶质细胞主要维持大脑的生理稳态。然而,在各种病理条件下,它们会发生形态、转录组和功能的转变,统称为反应性星形胶质细胞增生。最近的研究积累了一系列证据,表明反应性星形胶质细胞增生在阿尔茨海默病(AD)的病理过程中起关键作用。特别是单胺氧化酶B,一种主要在星形胶质细胞中表达的线粒体酶,在AD大脑的神经元功能障碍和神经退行性变中起重要作用。此外,据报道,在AD中,反应性星形胶质细胞增生先于其他病理特征,如淀粉样β斑块沉积和tau缠结形成。由于反应性星形胶质细胞发病早且对病理有深远影响,在过去十年中,人们广泛努力利用正电子发射断层扫描(PET)成像在AD患者大脑中可视化这些细胞。在这篇综述中,我们总结了关于反应性星形胶质细胞在AD中的重要病理意义及其作为PET成像靶点应用的最新研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c551/11196512/b117270dac86/13139_2023_837_Fig1_HTML.jpg

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