A new study from the Department of Pathology at Case Western Reserve University School of Medicine shows that the infectious version of prion proteins, the main culprits behind the human form of mad cow disease or variant Creutzfeldt-Jakob Disease (vCJD), are not destroyed by digestive enzymes found in the stomach. Furthermore, the study finds that the infectious prion proteins, also known as prions, cross the normally stringent intestinal barrier by riding piggyback on ferritin, a protein normally absorbed by the intestine and abundantly present in a typical meat dish. The study appears in the Dec. 15 issue of the Journal of Neuroscience.
Prions are a modified form of normal proteins, the prion proteins, which become infectious and accumulate in the nervous system causing fatal neurodegenerative disease. Variant CJD results from eating contaminated beef products from cattle infected with mad cow disease. To date, 155 cases of confirmed and probable vCJD in the world have been reported, and it is unclear how many others are carrying the infection.
According to the study's senior author Neena Singh, M.D., Ph.D., associate professor of pathology, little is known about the mechanism by which prions cross the human intestinal barrier, which can be a particularly difficult obstacle to cross.
"The mad cow epidemic is far from over, and the continuous spread of a similar prion disease in the deer and elk population in the U.S. raises serious public health concerns," said Singh. "It is therefore essential to understand how this disease is transmitted from one species to another, especially in the case of humans where the infectious prions survive through stages of cooking and digestion."
Using brain tissues infected with the spontaneously occurring version of CJD which is also caused by prions, the researchers simulated the human digestive process by subjecting the tissue to sequential treatment with digestive fluids as found in the human intestinal tract. They then studied how the surviving prions are absorbed by the intestine using a cell model. The prions were linked with ferritin, a cellular protein that normally binds excess cellular iron to store it in a soluble, non-toxic form within the cell.
"Since ferritin shares considerable similarity between species, it may facilitate the uptake of prions from distant species by the human intestine,"said Singh."This important finding provides insight into the cellular mechanisms by which infectious prions ingested with contaminated food cross the species barrier, and provides the possibility of devising practical methods for blocking its uptake," she said. "If we can develop a method of blocking the binding of prions to ferritin, we may be able to prevent animals from getting this disease through feed, and stop the transmission to humans."
Currently, Singh's group is checking whether prions from distant species such as deer and elk can cross the human intestinal barrier.
The study was supported by National Institutes of Health grants.
Materials provided by Case Western Reserve University. Note: Content may be edited for style and length.
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