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亚细胞区室中的谷胱甘肽动力学及其对药物开发的影响。

Glutathione dynamics in subcellular compartments and implications for drug development.

作者信息

Lin Hanfeng, Wang Lingfei, Jiang Xiqian, Wang Jin

机构信息

Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA; Center for NextGen Therapeutics, Baylor College of Medicine, Houston, TX 77030, USA.

Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA.

出版信息

Curr Opin Chem Biol. 2024 Aug;81:102505. doi: 10.1016/j.cbpa.2024.102505. Epub 2024 Jul 24.

Abstract

Glutathione (GSH) is a pivotal tripeptide antioxidant essential for maintaining cellular redox homeostasis and regulating diverse cellular processes. Subcellular compartmentalization of GSH underscores its multifaceted roles across various organelles including the cytosol, mitochondria, endoplasmic reticulum, and nucleus, each exhibiting distinct regulatory mechanisms. Perturbations in GSH dynamics contribute to pathophysiological conditions, emphasizing the clinical significance of understanding its intricate regulation. This review consolidates current knowledge on subcellular GSH dynamics, highlighting its implications in drug development, particularly in covalent drug design and antitumor strategies targeting intracellular GSH levels. Challenges and future directions in deciphering subcellular GSH dynamics are discussed, advocating for innovative methodologies to advance our comprehension and facilitate the development of precise therapeutic interventions based on GSH modulation.

摘要

谷胱甘肽(GSH)是一种关键的三肽抗氧化剂,对于维持细胞氧化还原稳态和调节多种细胞过程至关重要。GSH的亚细胞区室化突出了其在包括细胞质、线粒体、内质网和细胞核在内的各种细胞器中的多方面作用,每个细胞器都表现出独特的调节机制。GSH动态变化的扰动会导致病理生理状况,这凸显了理解其复杂调节的临床意义。本综述整合了关于亚细胞GSH动态变化的当前知识,强调了其在药物开发中的意义,特别是在共价药物设计和针对细胞内GSH水平的抗肿瘤策略方面。讨论了解析亚细胞GSH动态变化的挑战和未来方向,倡导采用创新方法来增进我们的理解,并促进基于GSH调节的精确治疗干预措施的开发。

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