Malformed prion proteins appear to be responsible for transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease. Large fibrillar deposits of these prions are found in the brain tissue of patients with this type of illness, but whether these deposits also cause disease is not clear. A study appearing in the 08 Sept. 2005 issue of Nature (Vol. 436, No. 7056, pp. 257-261) now shows that smaller, non-fibrillar clusters of between 14 to 28 prion molecules are by far the most infectious.
Byron Caughey and colleagues also reveal that groups of fewer than six such molecules have essentially no infectivity. Attempts to alleviate symptoms by destabilizing these large protein aggregates might make things worse by producing smaller but more infectious particles. These findings might have implications for the treatment of other afflictions such as Alzheimer's and Parkinson's disease, also characterized by deposition of amyloid fibrils.
In the same issue, the origins of infectious prion 'seeds' in yeast are explored in a paper by Tricia Serio and Prasanna Satpute-Krishnan (pp. 262-265). They demonstrate that the conversion of the yeast protein Sup35 to its prion form does not need to happen during the synthesis of Sup35 -mature and fully functional molecules can readily join a prion seed. This remodelling of mature protein is accompanied by the loss of its activity and therefore causes immediate effects in the cell.
Byron Caughey (NIAID/NIH Rocky Mountain Laboratories, Hamilton, MT, USA)
Tricia R. Serio (Brown University, Providence, RI, USA)
(C) Nature press release.
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