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基质金属蛋白酶与阿尔茨海默病病理生理学之间的联系

The Link Between Matrix Metalloproteinases and Alzheimer's Disease Pathophysiology.

作者信息

Radosinska Dominika, Radosinska Jana

机构信息

Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovak Republic.

Institute of Physiology, Faculty of Medicine, Comenius University in Bratislava, Sasinkova 2, 81372, Bratislava, Slovak Republic.

出版信息

Mol Neurobiol. 2025 Jan;62(1):885-899. doi: 10.1007/s12035-024-04315-0. Epub 2024 Jun 27.

Abstract

Alzheimer's disease (AD) is a major contributor to dementia and the most common neurodegenerative disorder. In AD pathophysiology, matrix metalloproteinases (MMPs)-proteolytic enzymes, best known to be responsible for remodeling and degradation of the extracellular matrix-were suggested to play an important role. Due to the diverse nature of the published data and frequent inconsistent results presented in available papers, it was considered essential to analyze all aspects of MMP literature with respect to AD pathophysiology and attempt to outline a unifying concept for understanding their role in AD. Thus, the main contribution of this review article is to summarize the most recent research on the participation of MMP in AD pathophysiology obtained using the cell cultures to understand the molecular principles of their action. Furthermore, an updated comprehensive view regarding this topic based exclusively on papers from human studies is provided as well. It can be concluded that determining the exact role of any particular MMPs in the AD pathophysiology holds promise for establishing their role as potential biomarkers reflecting the severity or progression of this disease or for developing new therapeutic agents targeting the processes that lead to AD.

摘要

阿尔茨海默病(AD)是导致痴呆的主要原因,也是最常见的神经退行性疾病。在AD的病理生理学中,基质金属蛋白酶(MMPs)——一种蛋白水解酶,最为人所知的是其负责细胞外基质的重塑和降解——被认为发挥着重要作用。由于已发表数据的多样性以及现有论文中频繁出现的不一致结果,对MMP文献中与AD病理生理学相关的所有方面进行分析,并尝试勾勒出一个统一的概念以理解它们在AD中的作用,被认为是至关重要的。因此,这篇综述文章的主要贡献在于总结了利用细胞培养获得的关于MMP参与AD病理生理学的最新研究,以了解其作用的分子原理。此外,还提供了一个仅基于人体研究论文的关于该主题的最新全面观点。可以得出结论,确定任何特定MMP在AD病理生理学中的确切作用,有望确立它们作为反映该疾病严重程度或进展的潜在生物标志物的作用,或用于开发针对导致AD的过程的新治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a1/11711632/94d76ae666c1/12035_2024_4315_Fig1_HTML.jpg

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