How does a prion make it all the way into the CNS?

So I'm having a hard time with this, because for years I have been saying that Glucosamine & Chondroitin are of no use because the intestines and stomach break them down before they would make it to any joint space. But Mad cow is a perfect example of a protein making it through a 4 chambered stomach into the intestines, past the liver, into the blood stream, past the blood-brain barrier and into the CNS, causing disease. How is this possible? It goes against my belief that 1) The largest protein break-down product that could be absorbed is short chain amino acids. And 2) The blood brain barrier is almost impervious.

Does it have to do with being absorbed with fatty acids?

Thanks and please provide further internet reading.

1 Answer

  • Anonymous
    9 years ago
    Favorite Answer

    Are you making an assumption about the passage of prion into the bloodstream?

    Because the pathogenic prion protein is misfolded, it may not be susceptible to normal proteolytic digestion in the gut. (Another example of a protein that won't be digested is keratin--you can't digest hair. Also there are polypeptide stretches of wheat gluten that won't be cleaved further.)

    The prion protein (and other things in the GI tract) are sampled by dendritic cells, and by M cells at the Peyer's patches in a process like endocytosis, which can bring in the protein wholesale for presentation to the immune system. The dendritic cells can carry this back to the lymph nodes and other immune cell types, and thus throughout the lymphatic system. Prion is normally expressed by immune cell types, so those prions could be converted to the pathogenic type. The CNS is immunologically priveleged, but it still falls under immune surveillance; immune cells bearing the pathogenic prion can enter.

    Also the nerves of the enteric nervous system of the gut can be exposed to the prion this way, and these nerves also express prions, so those prions can also be converted to the pathogenic form. The enteric nervous system can interact with the sympathetic and parasympathetic nervous system, and these hook up with the CNS.

    As for glucosamine, it is as simple as glucose, and that is transported as-is across the gut epithelia readily.

    As for chondroitin, apparently it is also bioavailable orally.

    The controversy with those lies with whether they can influence steady-state levels in the body, and whether it has any therapeutic effect in osteoarthritis.

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