Towards unfolding the prion misfolding mystery: Protein free radical chemistry in transmissible spongiform encephalopathies  

作　　者：YANG Chi-Ming( Neurochemlstry Group, College of Chemistry, Nankai University, Tianjin 300071 Institute for Life Sciences & Health, La Jolla (San Diego), CA 92039-2035, USA) 

出　　处：《Nuclear Science and Techniques》2003年第3期199-205,共7页核技术（英文）

基　　金：Supported partly by the National Natural Science Foundation of China(No.20042002)and the Ministry of Science and Technology of China

摘　　要：Owing to the high oxygen-respiration in the brain of mammals, oxidative damage to prion protein hasbeen suggested to be an additional factor. A large body of intriguing features of scrapie and prion diseases haveprovided multiple lines of indirect chemistry evidence, suggesting that the infectious agents may be putative forms ofsequence-specific prion radicals (SSPR) and/or their immediate precursors in the transmissible spongiform encepha-lopathies (TSE). Here a molecular mechanism corresponding to the self-replication of scrapie protein mediated byprion free-radical processes, consonant with "protein-only" hypotheses is proposed. This new theory may not onlyaid our understanding of the occurrence of prions, but also provides new insight into the possible chemistry principlesunderlying the neurodegenerative disorders. It is anticipated that future studies based on this suggestion and chem-istry principles of genetic diseases may allow us to determine an effective approach to stop mad cow disease and itshuman version, new variant of Creutzfeldt-Jakob disease (v CJD).Owing to the high oxygen-respiration in the brain of mammals, oxidative damage to prion protein has been suggested to be an additional factor. A large body of intriguing features of scrapie and prion diseases have provided multiple lines of indirect chemistry evidence, suggesting that the infectious agents may be putative forms of sequence-specific prion radicals (SSPR) and /or their immediate precursors in the transmissible spongiform encepha-lopathies (TSE). Here a molecular mechanism corresponding to the self-replication of scrapie protein mediated by prion free-radical processes, consonant with 'protein-only' hypotheses is proposed. This new theory may not only aid our understanding of the occurrence of prions, but also provides new insight into the possible chemistry principles underlying the neurodegenerative disorders. It is anticipated that future studies based on this suggestion and chemistry principles of genetic diseases may allow us to determine an effective approach to stop mad cow disease and its human version, new variant of Creutzfeldt-Jakob disease (v CJD).

关 键 词：蛋白感染素 蛋白质 海绵状脑病 遗传性疾病 克劳伊氏病 

分 类 号：S857.1[农业科学—临床兽医学]