Melatonin regulates mitochondrial dynamics and alleviates neuron damage in prion diseases
Melatonin regulates mitochondrial dynamics and alleviates neuron damage in prion diseases
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DOI：
10.18632/aging.103328
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发表时间：
2020-06
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通讯作者：
Xixi Zhang;Deming Zhao;Wei Wu;Syed Zahid Ali Shah;Mengyu Lai;Dongming Yang;Jie Li;Zhiling Guan;Wen Li;Hongli Gao;Huafen Zhao;Xiangmei Zhou;Lifeng Yang
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作者：
Xixi Zhang;Deming Zhao;Wei Wu;Syed Zahid Ali Shah;Mengyu Lai;Dongming Yang;Jie Li;Zhiling Guan;Wen Li;Hongli Gao;Huafen Zhao;Xiangmei Zhou;Lifeng Yang
朊病毒病是与动物和人类的神经元损伤和行为障碍相关的神经退行性疾病。褪黑激素是一种有效的抗氧化剂，用于治疗多种疾病。我们研究了褪黑激素对朊病毒诱导的N2 a细胞损伤的神经保护作用。用10 μM褪黑激素预处理N2 a细胞1小时，然后用100 μM PrP 106 -126孵育24小时。褪黑素可明显减轻PrP 106 -126诱导的N2 a细胞凋亡，并抑制PrP 106 -126诱导的线粒体异常和功能障碍，包括线粒体碎片化和活性氧（ROS）过度产生、ATP抑制、线粒体膜电位（MMP）降低以及线粒体动力蛋白动力蛋白相关蛋白1（DRP 1）和视神经萎缩蛋白1（OPA 1）改变。我们的研究结果表明，褪黑激素的预处理，防止有害的影响PrPSc对线粒体功能和动力学，保护突触和减轻神经元损伤。褪黑素可能成为治疗朊病毒病的一种新的有效药物。
Prion diseases are neurodegenerative diseases associated with neuron damage and behavioral disorders in animals and humans. Melatonin is a potent antioxidant and is used to treat a variety of diseases. We investigated the neuroprotective effect of melatonin on prion-induced damage in N2a cells. N2a cells were pretreated with 10 μM melatonin for 1 hour followed by incubation with 100 μM PrP106-126 for 24 hours. Melatonin markedly alleviated PrP106-126-induced apoptosis of N2a cells, and inhibited PrP106-126-induced mitochondrial abnormality and dysfunction, including mitochondrial fragmentation and overproduction of reactive oxygen species (ROS), suppression of ATP, reduced mitochondrial membrane potential (MMP), and altered mitochondrial dynamic proteins dynamin-related protein 1 (DRP1) and optic atrophy protein 1 (OPA1). Our findings identify that pretreatment with melatonin prevents the deleterious effects of PrPSc on mitochondrial function and dynamics, protects synapses and alleviates neuron damage. Melatonin could be a novel and effective medication in the therapy of prion diseases.