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

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

YANG Chi-Ming
Nuclear Science and TechniquesVol.14, No.3pp.199-205Published in print 01 Aug 2003
22900

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 encephalopathies (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).

Sequence-specific prion radicals (SSPR)Transmissible spongiform encephalopathy (TSE)Genetic diseasesCreutzfeldt-Jakob disease (CJD)Reductive zipper motifProtein-radical process
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