Content deleted Content added
No edit summary Tags: Mobile edit Mobile web edit |
Artoria2e5 (talk | contribs) |
||
Line 36:
The propagation of PrP<sup>Sc</sup> is a topic of great interest, as its accumulation is a pathological cause of [[neurodegeneration]]. Based on the progressive nature of spongiform encephalopathies, the predominant hypothesis posits that the change from normal PrP<sup>C</sup> is caused by the presence and interaction with PrP<sup>Sc</sup>.<ref name = "pmid21350487">{{cite journal | vauthors = Sandberg MK, Al-Doujaily H, Sharps B, Clarke AR, Collinge J | title = Prion propagation and toxicity in vivo occur in two distinct mechanistic phases | journal = Nature | volume = 470 | issue = 7335 | pages = 540–2 | date = February 2011 | pmid = 21350487 | doi = 10.1038/nature09768| bibcode = 2011Natur.470..540S }}</ref> Strong support for this is taken from studies in which ''PRNP''-knockout mice are resistant to the introduction of PrP<sup>Sc</sup>.<ref name = "pmid8100741">{{cite journal | vauthors = Büeler H, Aguzzi A, Sailer A, Greiner RA, Autenried P, Aguet M, Weissmann C | title = Mice devoid of PrP are resistant to scrapie | journal = Cell | volume = 73 | issue = 7 | pages = 1339–47 | date = July 1993 | pmid = 8100741 | doi = 10.1016/0092-8674(93)90360-3| doi-access = free }}</ref> Despite widespread acceptance of the conformation conversion hypothesis, some studies mitigate claims for a direct link between PrP<sup>Sc</sup> and [[cytotoxicity]].<ref name = "elusive">{{cite journal | vauthors = Aguzzi A, Baumann F, Bremer J | title = The prion's elusive reason for being | journal = Annu. Rev. Neurosci. | volume = 31 | issue = | pages = 439–77 | year = 2008 | pmid = 18558863 | doi = 10.1146/annurev.neuro.31.060407.125620}}</ref>
[[Polymorphism (biology)|Polymorphisms]] at sites 136, 154, and 171 are associated with varying susceptibility to ovine [[scrapie]]. (These ovine sites correspond to human sites 133, 151, and 168.) Polymorphisms of the PrP-VRQ form and PrP-ARQ form are associated with increased susceptibility, whereas PrP-ARR is associated with resistance. The National Scrapie Plan of the UK aims to breed out these scrapie polymorphisms by increasing the frequency of the resistant allele.<ref>{{cite journal | vauthors = Atkinson M | title = National scrapie plan | journal = The Veterinary Record | volume = 149 | issue = 15 | pages = 462 | date = October 2001 | pmid = 11688751 }}</ref> However, PrP-ARR polymorphisms are susceptible to atypical scrapie, so this may prove unfruitful.
== Function ==
| |||