Chen Shang-Der, Yang Jenq-Lin, Lin Tsu-Kung, Yang Ding-I
Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City 83301, Taiwan.
Institute for Translation Research in Biomedicine; Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City 83301, Taiwan.
J Clin Med. 2019 Jul 9;8(7):1001. doi: 10.3390/jcm8071001.
Low levels of reactive oxygen species (ROS) are critical for the operation of regular neuronal function. However, heightened oxidative stress with increased contents of oxidation markers in DNA, lipids, and proteins with compromised antioxidant capacity may play a harmful role in the brain and may be implicated in the pathophysiology of neurodegenerative diseases. Sestrins, a family of evolutionarily-conserved stress-inducible proteins, are actively regulated by assorted stresses, such as DNA damage, hypoxia, and oxidative stress. Three highly homologous genes that encode sestrin1, sestrin2, and sestrin3 proteins exist in the genomes of vertebrates. Under stressful conditions, sestrins are activated with versatile functions to cope with different types of stimuli. A growing body of evidence suggests that sestrins, especially sestrin2, can counteract oxidative stress, lessen mammalian/mechanistic target of rapamycin (mTOR) expression, and promote cell survival, thereby playing a critical role in aging-related disorders including neurodegeneration. Strategies capable of augmenting sestrin expression may; thus, facilitate cell adaptation to stressful conditions or environments through stimulation of antioxidant response and autophagy process, which may carry clinical significance in neurodegenerative diseases.
低水平的活性氧（ROS）对于正常神经元功能的运作至关重要。然而，氧化应激加剧，DNA、脂质和蛋白质中的氧化标志物含量增加，同时抗氧化能力受损，这可能会对大脑产生有害作用，并可能与神经退行性疾病的病理生理学有关。Sesrins是一类进化上保守的应激诱导蛋白家族，受到各种应激（如DNA损伤、缺氧和氧化应激）的积极调控。脊椎动物基因组中存在三个高度同源的基因，分别编码Sesrin1、Sesrin2和Sesrin3蛋白。在应激条件下，Sesrins被激活并具有多种功能以应对不同类型的刺激。越来越多的证据表明，Sesrins，尤其是Sesrin2，可以对抗氧化应激，降低哺乳动物/雷帕霉素靶蛋白（mTOR）的表达，并促进细胞存活，从而在包括神经退行性变在内的与衰老相关的疾病中发挥关键作用。因此，能够增强Sesrin表达的策略可能通过刺激抗氧化反应和自噬过程来促进细胞适应应激条件或环境，这可能在神经退行性疾病中具有临床意义。
