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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Prion diseases: what is the neurotoxic molecule?

A great deal of effort has been devoted during the past 20 years to defining the chemical nature of prions, the infectious agents responsible for transmissible spongiform encephalopathies. In contrast, much less attention has been paid to elucidating how prions actually damage the central nervous system. Although it is commonly assumed that PrP(Sc), the protein constituent of infectious prions, is the primary culprit, increasing evidence indicates that this may not be the case. Several alternative molecular forms of PrP are reasonable candidates for the neurotoxic species in prion diseases, although it is still too early to tell whether these or other ones will turn out to be the true instigating factors. The cellular pathways activated by neurotoxic forms of PrP that ultimately result in neuronal death are also being investigated, and several possible mechanisms have been uncovered, including the operation of quality control processes in the endoplasmic reticulum. Elucidating the distinction between the infectious and neurotoxic forms of PrP has important implications for designing therapy of prion diseases, as well as for understanding pathogenic mechanisms operative in other neurodegenerative disorders and the role of prion-like states in biology.[1]


  1. Prion diseases: what is the neurotoxic molecule? Chiesa, R., Harris, D.A. Neurobiol. Dis. (2001) [Pubmed]
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