Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnocentric of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563003, China.
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnocentric of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563003, China.
Biomed Pharmacother. 2020 Dec;132:110928. doi: 10.1016/j.biopha.2020.110928. Epub 2020 Oct 28.
Sirtuin-3 (SIRT3) is a NAD-dependent protein deacetylase that is located in mitochondria, regulating mitochondrial proteins and maintaining cellular antioxidant status. Increasing evidence demonstrates that SIRT3 plays a role in degenerative disorders including Parkinson's disease (PD), which is a devastating nervous system disease currently with no effective treatments available. Although the etiology of PD is still largely ambiguous, substantial evidence indicates that mitochondrial dysfunction and oxidative stress play major roles in the pathogenesis of PD. The imbalance of reactive oxygen species (ROS) production and detoxification leads to oxidative stress that can accelerate the progression of PD. By causing conformational changes in the deacetylated proteins SIRT3 modulates the activities and biological functions of a variety of proteins involved in mitochondrial antioxidant defense and various mitochondrial functions. Increasingly more studies have suggested that upregulation of SIRT3 confers beneficial effect on neuroprotection in various PD models. This review discusses the mechanism by which SIRT3 regulates intracellular oxidative status and mitochondrial function with an emphasis in discussing in detail the regulation of SIRT3 on each component of the five complexes of the mitochondrial respiratory chain and mitochondrial antioxidant defense, as well as the pharmacological regulation of SIRT3 in light of therapeutic strategies for PD.
Sirtuin-3 (SIRT3) 是一种 NAD 依赖性蛋白去乙酰化酶，位于线粒体中，调节线粒体蛋白并维持细胞抗氧化状态。越来越多的证据表明，SIRT3 在退行性疾病中发挥作用，包括帕金森病 (PD)，这是一种目前尚无有效治疗方法的毁灭性神经系统疾病。尽管 PD 的病因仍在很大程度上不清楚，但大量证据表明线粒体功能障碍和氧化应激在 PD 的发病机制中起主要作用。活性氧 (ROS) 产生和解毒的失衡导致氧化应激，从而加速 PD 的进展。SIRT3 通过使去乙酰化蛋白发生构象变化，调节参与线粒体抗氧化防御和各种线粒体功能的多种蛋白的活性和生物学功能。越来越多的研究表明，SIRT3 的上调对各种 PD 模型中的神经保护具有有益作用。本综述讨论了 SIRT3 调节细胞内氧化状态和线粒体功能的机制，并详细讨论了 SIRT3 对线粒体呼吸链五复合物和线粒体抗氧化防御每个组成部分的调节，以及 SIRT3 的药理学调节根据 PD 的治疗策略。
