Cellular Prion Protein (PrPC) of the Neuron Cell Transformed to a PK-Resistant Protein Under Oxidative Stress, Comprising Main Mitochondrial Damage in Prion Diseases
Cellular Prion Protein (PrPC) of the Neuron Cell Transformed to a PK-Resistant Protein Under Oxidative Stress, Comprising Main Mitochondrial Damage in Prion Diseases
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DOI：
10.1007/s12031-013-0008-6
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发表时间：
2013-05
影响因子：
3.1
通讯作者：
Fangzhong Yuan;Lifeng Yang;Zhuming Zhang;Wenyu Wu;Xiangmei Zhou;Xiaomin Yin;Deming Zhao
中科院分区：
文献类型：
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作者：
Fangzhong Yuan;Lifeng Yang;Zhuming Zhang;Wenyu Wu;Xiangmei Zhou;Xiaomin Yin;Deming Zhao
朊病毒疾病是一类致命的神经退行性疾病的特征。尽管越来越多的报告表明氧化应激在朊病毒疾病的进展中起着重要作用，但人们对氧化应激是朊病毒疾病的原因还是结果知之甚少。朊病毒病发生的机制也仍不清楚。本研究的目的是调查三件事：神经元细胞损伤的可能机制、抗蛋白酶 K (PK) PrPSc 的构象以及氧化应激在朊病毒疾病进展中的作用。研究结果表明，在 PrP106-126 存在的情况下，正常 PrPC 在氧化应激下转化为 PK 抗性蛋白。此外，蛋白质错误折叠的循环扩增过程可能加速了这一过程。本研究还观察到朊病毒疾病进展中的线粒体损伤和功能障碍。我们的结果表明神经元细胞损伤，特别是线粒体损伤，是由氧化应激引起的。这种损害可能是特定朊病毒病的最初原因。
Prion diseases characterize a category of fatal neurodegenerative diseases. Although reports have increasingly shown that oxidative stress plays an important role in the progression of prion diseases, little is known about whether oxidative stress is a cause or a consequence of a prion disease. The mechanism of prion disease development also remains unclear. The purpose of this study was to investigate three things: the possible mechanisms of neuron cell damage, the conformation of anti-protease K (PK) PrPSc, and the role of oxidative stress in the progression of prion diseases. The study results demonstrated that normal PrPCtransformed into a PK-resistant protein under oxidative stress in the presence of PrP106–126. Further, the protein misfolding cyclic amplification procedure may have accelerated this process. Mitochondrial damage and dysfunction in prion disease progression were also observed in this study. Our results suggested that neuron cell damage, and particularly mitochondrial damage, was induced by oxidative stress. This damage may be the initial cause of a given prion disease.