Fondazione Santa Lucia IRCCS, Rome, Italy.
Fondazione Santa Lucia IRCCS, Rome, Italy; Institute for Cell Biology and Neurobiology, CNR, Rome, Italy.
Neurochem Int. 2017 Oct;109:184-192. doi: 10.1016/j.neuint.2017.04.012. Epub 2017 Apr 25.
The NAD-dependent deacetylase protein Sirtuin 3 (SIRT3) is emerging among the factors playing a key role in the regulation of mitochondrial function and in the prevention of oxidative stress. This deacetylase activates protein substrates directly involved in the production and detoxification of ROS, such as superoxide dismutase 2 and catalase, but also enzymes in the lipid beta-oxidation pathway. In this paper we review existing evidence on the role of SIRT3 in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington disease, including data from new experiments in a model for amyotrophic lateral sclerosis linked to mutations in superoxide dismutase 1. Specifically, we report that expression of the mitochondrial isoform of SIRT3 is altered in muscle from the G93A-SOD1 mice during progression of disease; this alteration influences mitochondrial metabolism, which may be relevant for the well known energetic alterations taking place in ALS patients. These data reinforce the concept that SIRT3 may be a relevant therapeutic target is ALS as well as in other neurodegenerative diseases.
NAD 依赖性去乙酰化酶蛋白 Sirtuin 3（SIRT3）是一种在调节线粒体功能和预防氧化应激方面起关键作用的因子。这种去乙酰化酶可激活直接参与 ROS 产生和解毒的蛋白质底物，如超氧化物歧化酶 2 和过氧化氢酶，还可激活脂类β-氧化途径中的酶。本文综述了 SIRT3 在神经退行性疾病（如阿尔茨海默病、帕金森病和亨廷顿病）中的作用的现有证据，包括与超氧化物歧化酶 1 突变相关的肌萎缩侧索硬化症模型中的新实验数据。具体而言，我们报告在疾病进展过程中，G93A-SOD1 小鼠的肌肉中 SIRT3 的线粒体同工型表达发生改变；这种改变影响线粒体代谢，这可能与 ALS 患者中已知的能量改变有关。这些数据加强了这样一种观点，即 SIRT3 可能是 ALS 以及其他神经退行性疾病的一个有治疗意义的靶点。
