Prion protein oligomer and its neurotoxicity  

作　　者：Pei Huang Fulin Lian Yi Wen Chenyun Guo Donghai Lin 

机构地区：[1]School of Life Science and Technology, China Pharmaceutical University, Nanjing 21009, China [2]Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China [3]Key Laboratory of Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005 China

出　　处：《Acta Biochimica et Biophysica Sinica》2013年第6期442-451,共10页生物化学与生物物理学报（英文版）

基　　金：Funding This work was supported by the grants from the National Natural Science Foundation of China （Nos. 31170717, 91129713, and 30900233）.

摘　　要：The prion diseases, also known as transmissible spongiform encephalopathies, are fatal neurodegenerative disorders. According to the ＇protein only＇ hypothesis, the key molecular event in the pathogenesis of priori disease is the conformational conversion of the host-derived cellular prion protein （PrPc） into a misfolded form （scrapie PrP, prpSC）. Increasing evidence has shown that the most infectious factor is the smaller subfibrillar oligomers formed by prion proteins. Both the prion oligomer and PrPsc are rich in β-sheet structure and resistant to the proteolysis of pro- teinase K. The prion oligomer is soluble in physiologic environments whereas PrPsc is insoluble. Various prion oligomers are formed in different conditions. Prion oligomers exhibited more neurotoxicity both in vitro and in vivo than the fibrillar forms of PrPsc, implying that prion oligo- mers could be potential drug targets for attacking prion diseases. In this article, we describe recent experimental evidence regarding prion oligomers, with a special focus on prion oligomer formation and its neurotoxicity.The prion diseases, also known as transmissible spongiform encephalopathies, are fatal neurodegenerative disorders. According to the ＇protein only＇ hypothesis, the key molecular event in the pathogenesis of priori disease is the conformational conversion of the host-derived cellular prion protein （PrPc） into a misfolded form （scrapie PrP, prpSC）. Increasing evidence has shown that the most infectious factor is the smaller subfibrillar oligomers formed by prion proteins. Both the prion oligomer and PrPsc are rich in β-sheet structure and resistant to the proteolysis of pro- teinase K. The prion oligomer is soluble in physiologic environments whereas PrPsc is insoluble. Various prion oligomers are formed in different conditions. Prion oligomers exhibited more neurotoxicity both in vitro and in vivo than the fibrillar forms of PrPsc, implying that prion oligo- mers could be potential drug targets for attacking prion diseases. In this article, we describe recent experimental evidence regarding prion oligomers, with a special focus on prion oligomer formation and its neurotoxicity.

关 键 词：PRION OLIGOMER NEUROTOXICITY transmissiblespongiform encephalopathies 

分 类 号：S852.659.7[农业科学—基础兽医学] X503.1[农业科学—兽医学]