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How does the PrP scrapie protein maintain its confirmation while going through the GI tract? How does the PrP scrapie protein cross the blood brain barrier?

Wouldn't the host immune system recognize the prion as "not self" and attack it?

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    $\begingroup$ Googling your title question gets about 231,000 results. What specifically are you having difficulty with? $\endgroup$ – anongoodnurse Jun 4 '17 at 2:47
  • $\begingroup$ hmm idk how to be more specific but i guess I could say: "what structural part of the PrP scrappie protein provides it transport across the blood brain barrier ?" $\endgroup$ – Confusedbyeverything Jun 4 '17 at 3:08
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    $\begingroup$ @anongoodnurse The vast majority of the results (56k without quotes, only 3 if you put quotes) are just combinations of some of those keywords. The very few results that actually do say that prions cross the blood-brain barrier just do that, like this one, whithout explaining how. That's what OP is asking. By the way, just for you to understand how search engines can be complicated (or even skewed), in my country (Australia) this very SE question is result number 3 in Google right now. $\endgroup$ – user24284 Jun 4 '17 at 4:28
  • $\begingroup$ The link you provided raises more questions than it answers.. I dont see why we cant vaccinate against prions (or maybe just parts of it) if they spend so much time in secondary lymphoid organs? $\endgroup$ – Confusedbyeverything Jun 4 '17 at 5:38
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    $\begingroup$ @Confusedbyeverything You're literally confused! That link I shared was not for you, but for Anongoodnurse, showing that most sources we find online only affirm that prions cross the barriers without explaining how they do that. I didn't shared that link trying to provide an answer. $\endgroup$ – user24284 Jun 4 '17 at 8:35
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I am not sure if a perfect answer is possible owing to the fact that Prion diseases are still incompletely understood, and are actively under research. On a preliminary search, I found some papers which address the issue (cited at the end).

  • Since $PrP^C$ is normally found in the body, its role and its transport is also relevant to the issue. It seems to undergo bidirectional transport across the BBB using a saturable mechanism, mostly a specific transporter (1). It is taken up peripherally, and by several regions of the brain with the possibility that it is involved in various brain functions including modulating the BBB itself. Amyloid Beta-protein, with several kinetic and dynamic similarities with $PrP^C$, is shown to have BBB altering effects. (2) How far do the pathological prions follow this is seemingly unknown.
  • Autonomic nerves seem to play a role in their transport.(3) When challenged with prions, sympathectomy delays or even prevents the disease, whereas sympathetic hyperinnervation accelerates prion pathogenesis. There have been studies to elucidate the transport via the nerves, such as (4) and (5).

There are several other studies on this issue, and following the cited references might help you find them.

Reference number 3 also has information on the immunological response to prions.

References:

  1. Banks WA, Robinson SM, Diaz-Espinoza R, Urayama A, Soto C. Transport of prion protein across the blood–brain barrier. Experimental neurology. 2009 Jul 31;218(1):162-7.
  2. Giri R, Shen Y, Stins M, Du Yan S, Schmidt AM, Stern D, Kim KS, Zlokovic B, Kalra VK: Am J Physiol Cell Physiol. 2000 Dec; 279(6):C1772-81.
  3. Aguzzi A, Zhu C. Five questions on prion diseases. PLoS Pathog. 2012 May 3;8(5):e1002651.
  4. McBride PA, Schulz-Schaeffer WJ, Donaldson M, Bruce M, Diringer H, Kretzschmar HA, Beekes M. Early spread of scrapie from the gastrointestinal tract to the central nervous system involves autonomic fibers of the splanchnic and vagus nerves. Journal of virology. 2001 Oct 1;75(19):9320-7.
  5. Glatzel M, Heppner FL, Albers KM, Aguzzi A. Sympathetic innervation of lymphoreticular organs is rate limiting for prion neuroinvasion. Neuron. 2001 Jul 19;31(1):25-34.
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  • $\begingroup$ Thanks for the answer satwik, it certainly provided me with a lot more of an understanding than before. $\endgroup$ – Confusedbyeverything Jun 15 '17 at 21:00
  • $\begingroup$ 'bidirectional transport'? $\endgroup$ – Mockingbird Jul 11 '17 at 14:43

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