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New evidence questions the simple link between prion proteins and madcow disease

While newly published research confirms that under laboratory circumstances prion-protein can be absorbed across the gut, it also shows that this is unlikely to occur in real life. In addition, the results show that the places in the gut that do take up these disease-associated proteins are different from the locations where infectivity is known to be amplified. The findings will be published in the Journal of Pathology.

Since the outbreak of BSE in cattle and vCJD in humans, scientists have struggled to make sense of how an abnormal variation of a normal protein can trigger an infectious disease. Some are questioning whether this simple relationship exists at all. This paper adds new evidence that can inform the debate.

Firstly, it is known that individual people and animals have different levels of genetic susceptibility to this group of diseases, but no one knows how this resistance is achieved. One option is that resistant people do not absorb the disease-associated prion protein (PrP) from their guts.

To test this, the researchers worked with 50 sheep, with different degrees of genetic resistance to scrapie ?the sheep form of the disease. When they injected material containing abnormal prion protein (PrP) into the sheep's gut, it was equally absorbed by all sheep.

"This clearly shows that resistance is not achieved by blocking uptake of abnormal proteins from the gut ?it must be achieved by some other mechanism," says lead author Dr Martin Jeffrey.

Secondly, they looked in more detail at the route of absorption in the gut. Using surgically modified sheep, they loaded a small area of the gut with a fluid mixture containing 0.5 grams of scrapie infected brain containing a large amount of the disease specific variant of the PrP protein and watched how it was taken up. They saw the abnormal PrP was rapidly taken up by finger-like projections called villi and passed in to the lymph. It was not, however, taken up by structur
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Source:John Wiley & Sons, Inc.


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