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Scripps Research scientists show prions mutate and adapt to host environment
Date:12/17/2010

peutic target than its abnormal toxic relation.

"Because prions can adapt to changing environments, it now becomes clear that it will be more difficult than originally thought to find drugs that will work against them," Weissmann said. "But if you could develop a drug that inhibits formation of the normal prion protein, you could, in essence, starve the infectious prions and prevent them from reproducing. This approach to treatment, although technically demanding, can be envisaged because, as we have shown earlier, deprivation of PrP is not detrimental to health at least to the health of mice."

Folding and Misfolding

Prions, which are composed solely of protein, are classified by distinct strains, characterized by their incubation time and the disease they cause. In addition to BSE/mad cow disease in cattle, diseases caused by prions include scrapie in sheep, chronic wasting disease in deer, and variant Creutzfeldt-Jakob disease in humans. Prions have the ability to reproduce, despite the fact that they contain no nucleic acid genome.

Mammalian cells normally produce cellular prion protein or PrPC. During infection, abnormal or misfolded protein known as PrPSc converts the normal host prion protein into its toxic form by changing its conformation or shape. The end-stage consists of large sheets (polymers) of these misfolded proteins, which causes massive tissue and cell damage.

"The infectious prion protein can fold in different ways, and depending on the fold, a different prion strain results," Weissmann said. "As long as prions are maintained in the same host, they retain their characteristic fold, so that strains breed true."

When prions multiply, however, that fold is not always reproduced correctly, so a prion population contains many variants, albeit at low levels.

The new study found that when a prion population is transferred to a different host, one of the variants may replicat
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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert

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