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将自噬作为药物发现和治疗调节的策略。

Targeting autophagy as a strategy for drug discovery and therapeutic modulation.

作者信息

Gao Lixia, Jauregui Catherine E, Teng Yong

机构信息

Department of Oral Biology, Dental College of Georgia, Augusta University, Augusta, GA 30912, USA.

Georgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.

出版信息

Future Med Chem. 2017 Mar;9(3):335-345. doi: 10.4155/fmc-2016-0210. Epub 2017 Feb 8.

Abstract

Autophagy is a self-protective mechanism of living cells or organisms under various stress conditions. Studies of human genetics and pathophysiology have implicated that alterations in autophagy affect the context of cellular homeostasis and disease-associated phenotypes. The molecular components of autophagy are currently being explored as new pharmacologic targets for drug development and therapeutic intervention of various diseases. Drugs that restore the normal autophagic pathways have the potential for effectively treating human disorders that depend on aberrations of autophagy. Here, we review the role of autophagy and its alterations in the pathogenesis of diverse diseases, and drug discovery strategies for modulating autophagy for therapeutic benefits as well as possible safety concerns and caveats associated with such approaches.

摘要

自噬是活细胞或生物体在各种应激条件下的一种自我保护机制。人类遗传学和病理生理学研究表明,自噬的改变会影响细胞稳态和疾病相关表型的背景。目前正在探索自噬的分子成分,作为药物开发和各种疾病治疗干预的新药理学靶点。恢复正常自噬途径的药物有可能有效治疗依赖自噬异常的人类疾病。在这里,我们综述了自噬及其改变在多种疾病发病机制中的作用,以及调节自噬以获得治疗益处的药物发现策略,以及与此类方法相关的可能的安全问题和注意事项。

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