title: Cellular prion protein (PrPC) of the neuron cell transformed to a PK-resistant protein under oxidative stress, comprising main mitochondrial damage in prion diseases.
abstract: 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) PrP(Sc), and the role of oxidative stress in the progression of prion diseases. The study results demonstrated that normal PrP(C) transformed 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.
authors.affiliation: State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
authors.forename: Fangzhong
authors.initials: F
authors.lastname: Yuan
authors.forename: Lifeng
authors.initials: L
authors.lastname: Yang
authors.forename: Zhuming
authors.initials: Z
authors.lastname: Zhang
authors.forename: Wenyu
authors.initials: W
authors.lastname: Wu
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Zhou
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Yin
authors.forename: Deming
authors.initials: D
authors.lastname: Zhao
mesh_terms: D045744:Cell Line, Tumor; D019286:Endopeptidase K / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D017096:Prion Diseases / Q000378:metabolism*; D011328:Prions / Q000378:metabolism* / Q000494:pharmacology; D017510:Protein Folding
chemical_list: D010446:Peptide Fragments; D011328:Prions; C082632:prion protein (106-126); D007501:Iron; D019286:Endopeptidase K