Prions, the protein-like pathogens at the heart of the fatal brain disorder CJD, so-called mad cow disease, and related diseases can rapidly "remodel" good proteins into bad, according to US scientists, who have demonstrated this for the first time in living cells.

The encephalopathic diseases, Creutzfeldt-Jakob disease (CJD) and kuru in humans, together with scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, and other diseases, are caused by errant strands of protein-like material known as prions, which replicate by re-modeling healthy proteins into copies of themselves when they come into contact with them.

Now, two Brown Medical School biologists, Prasanna Satpute-Krishnan and Tricia Serio, have figured out details of the fate of healthy protein when it comes into contact with Sup35, a yeast protein similar to the human prion protein PrP. The researchers describe this reproductive maneuver in clearer detail than ever before and shed light on how prions function. Their findings add to our growing understanding of prion diseases and in the long-term might help in the search for treatments.

The researchers tagged the non-prion form of Sup35 with green fluorescent protein in one group of cells and "mated" these cells with another group that contained the prion form. When the two forms came into contact in the same cell, the fluorescent protein was distorted so that it produced a different pattern of fluorescence, suggesting it had been converted into the prion form.

The researchers state they are the first team to observe this remodeling in live cells. However, Satpute-Krishnan explains that the surprising aspect of their results is the speed with which protein conversion took place. "The prions were taking all the existing protein and refolding it immediately," she explains, "It's a very, very rapid change."

"Our studies provide some insight into how the appearance of a misfolded protein - a rare event - can lead to devastating neurological diseases," said Serio. "Just a small amount of prion-state protein can rapidly convert healthy protein into a pathogenic form."

Despite the conversion, the "infected" yeast cells still function fairly normally, although they have several new characteristics, such as the ability to withstand chemical and environmental stresses more effectively. This survival boost supports the theory that prions endured evolution because they confer an advantage on cells allowing them to adapt to rapidly changing conditions. The flipside is that in the long-term the infected individual may die of an encephalopathy.

Similar protein self-replication is seen in neurodegenerative disorders, such as Alzheimer's, Parkinson's, and Huntington's diseases and so might provide new insights into these too.