Health and Medicine Question #8863

Charlie, a 21 year old male from Astana, kazakhstan asks on December 14, 2012,

How are prions able to infect someone's brain after they are eaten? Prions are proteins and large proteins are denatured and chopped up when digested. Even if prions did not get degraded in the gastrointestinal tract how could such a large protein be absorbed in the gut and then even pass the blood brain barrier? It seems impossible.

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The answer

Barry Shell answered on December 14, 2012

Despite the point you make about digestion, the particular protein structure of prions appears to be extremely stable and immune from digestion processes. See this paper in pubmed, which shows that prions pass completely through the digestive system of animals. A deeper literature search would likely uncover papers that go into detail about the amino acid structure of prions and their specific folding and how these factors give it the stability required to make it through the digestive tract and still be infective. Other research shows that even if the protein is degraded to some extent, as long as a crucial part of the prion protein remains stable, then it can cause the whole prion molecule to reform later after it gets into the brain, by making use of local biochemical pathways.

Another way to answer this is: we don't know. It appears that a fair bit about prion infection is poorly understood. However, the paper cited above is only one of many that have shown that prions can survive the digestive system.

Neil Cashman, UBC professor of medicine and Scientific Director of PrioNet Canada answered on December 15, 2012

One thing I might add is that prions can actually infect gut lymphoid cells and "M-cells" lining the gut, so there is actually no requirement for them to pass into digestive pathways.

We think we understand neuropathogenesis [how the disease originates and develops in the nervous system] as 1) local infection of gut; 2) retrograde transport of infectious prions to the brainstem via autonomic innervation of the gut; and 3) local propagation of prions in the brain. 

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