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药物重定位:小分子对抗 Cu(II)-淀粉样β和自由基。

Drug repurposing: small molecules against Cu(II)-amyloid-β and free radicals.

机构信息

Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.

Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.

出版信息

J Inorg Biochem. 2021 Nov;224:111592. doi: 10.1016/j.jinorgbio.2021.111592. Epub 2021 Aug 27.

Abstract

Alzheimer's disease (AD) presents a complex pathology entangling numerous pathological factors, including amyloid-β (Aβ), metal ions, and reactive oxygen species (ROS). Increasing evidence reveals pathological connections among these distinct components in AD. For instance, the association between the amyloid cascade and metal ion hypotheses has introduced a novel pathogenic target: metal-bound Aβ. Investigation of such interconnections requires substantial research and can be expedited by chemical reagents that are able to modify multiple pathogenic factors in AD. Drug repurposing is an efficient approach for rediscovering previously utilized molecules with desirable biological and pharmaceutical properties as chemical reagents. Herein, we report the evaluation of three pre-approved drug molecules, selected based on their chemical structure and properties, as chemical reagents that can be used for elucidating the complicated pathology of AD.

摘要

阿尔茨海默病(AD)呈现出复杂的病理学,涉及许多病理因素,包括淀粉样蛋白-β(Aβ)、金属离子和活性氧物种(ROS)。越来越多的证据揭示了 AD 中这些不同成分之间的病理联系。例如,淀粉样蛋白级联和金属离子假说之间的关联引入了一个新的致病靶点:金属结合的 Aβ。研究这些相互联系需要大量的研究,而能够修饰 AD 中多种致病因素的化学试剂可以加速这一进程。药物再利用是一种有效的方法,可以重新发现具有理想生物学和药物特性的先前使用的分子作为化学试剂。在此,我们报告了三种预先批准的药物分子的评估,这些分子是根据它们的化学结构和性质选择的,作为可以用于阐明 AD 复杂病理学的化学试剂。

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