Editing Prion (section)

== Transmissible spongiform encephalopathies ==
{{Main|Transmissible spongiform encephalopathy}}
{| class = "wikitable floatright" style = "font-size:90%"
|+Diseases caused by prions
|-
! width="130" |Affected animal(s)
! width="250" |Disease
|-
|[[Domestic sheep|Sheep]], [[Goat]]
|[[Scrapie]]<ref name="ictvdb-prions">{{cite web | url=https://www.ncbi.nlm.nih.gov/ICTVdb/Ictv/fs_prion.htm | title=90. Prions | work=ICTVdB Index of Viruses | publisher=U.S. National Institutes of Health website | date=2002-02-14 | access-date=2010-02-28 | archive-date=2009-08-27 | archive-url=https://web.archive.org/web/20090827131816/http://www.ncbi.nlm.nih.gov/ICTVdb/Ictv/fs_prion.htm | url-status=live }}</ref>
|-
|[[Cattle]]
|[[Bovine spongiform encephalopathy]]<ref name="ictvdb-prions" />
|-
|[[Camel]]<ref>{{cite journal | vauthors = Babelhadj B, Di Bari MA, Pirisinu L, Chiappini B, Gaouar SB, Riccardi G, Marcon S, Agrimi U, Nonno R, Vaccari G | title = Prion Disease in Dromedary Camels, Algeria | journal = Emerging Infectious Diseases | volume = 24 | issue = 6 | pages = 1029–36 | date = June 2018 | pmid = 29652245 | pmc = 6004840 | doi = 10.3201/eid2406.172007 }}</ref>
|[[Camel spongiform encephalopathy]] (CSE)
|-
|[[Mink]]<ref name="ictvdb-prions" />
|[[Transmissible mink encephalopathy]] (TME)
|-
|[[White-tailed deer]], [[elk]], [[mule deer]], [[moose]]<ref name="ictvdb-prions" />
|[[Chronic wasting disease]] (CWD)
|-
|[[Cat]]<ref name="ictvdb-prions" />
|[[Feline spongiform encephalopathy]] (FSE)
|-
|[[Nyala]], [[Oryx]], [[Greater Kudu]]<ref name="ictvdb-prions" />
|[[Exotic ungulate encephalopathy]] (EUE)
|-
|[[Ostrich]]<ref name="hussein2004">{{cite journal |vauthors=Hussein MF, Al-Mufarrej SI |year=2004 |url=https://apps.kfu.edu.sa/sjournal/ara/pdffiles/b526.pdf |title=Prion Diseases: A Review; II. Prion Diseases in Man and Animals |journal=Scientific Journal of King Faisal University (Basic and Applied Sciences) |issue=2 |page=139 |access-date=April 9, 2016 |volume=5 |archive-date=April 21, 2016 |archive-url=https://web.archive.org/web/20160421204236/https://apps.kfu.edu.sa/sjournal/ara/pdffiles/b526.pdf |url-status=live }}</ref>
|Spongiform encephalopathy<br />(unknown if transmissible)
|-
|rowspan=10|Human
|[[Creutzfeldt–Jakob disease]] (CJD)<ref name="ictvdb-prions" />
|-
|[[Iatrogenesis|Iatrogenic]] Creutzfeldt–Jakob disease (iCJD)
|-
|[[Variant Creutzfeldt–Jakob disease]] (vCJD)
|-
|Familial Creutzfeldt–Jakob disease (fCJD)
|-
|Sporadic Creutzfeldt–Jakob disease (sCJD)
|-
|[[Gerstmann–Sträussler–Scheinker syndrome]] (GSS)<ref name="ictvdb-prions" />
|-
|[[Fatal insomnia]] (FFI)<ref>{{cite journal | vauthors = Mastrianni JA, Nixon R, Layzer R, Telling GC, Han D, DeArmond SJ, Prusiner SB | title = Prion protein conformation in a patient with sporadic fatal insomnia | journal = The New England Journal of Medicine | volume = 340 | issue = 21 | pages = 1630–8 | date = May 1999 | pmid = 10341275 | doi = 10.1056/NEJM199905273402104 | doi-access = free }}<br />Lay summary: {{cite web |title=BSE proteins may cause fatal insomnia |url=http://news.bbc.co.uk/2/hi/health/355297.stm |date=May 28, 1999|website=BBC News}}</ref>
|-
|[[Kuru (disease)|Kuru]]<ref name="ictvdb-prions" />
|-
| <!---Familiar spongiform encephalopathy associated with a novel prion protein gene mutation--->Familial spongiform encephalopathy<ref>{{cite journal | vauthors = Nitrini R, Rosemberg S, Passos-Bueno MR, da Silva LS, Iughetti P, Papadopoulos M, Carrilho PM, Caramelli P, Albrecht S, Zatz M, LeBlanc A | title = Familial spongiform encephalopathy associated with a novel prion protein gene mutation | journal = Annals of Neurology | volume = 42 | issue = 2 | pages = 138–146 | date = August 1997 | pmid = 9266722 | doi = 10.1002/ana.410420203 | s2cid = 22600579 }}</ref>
|-
|[[Variably protease-sensitive prionopathy]] (VPSPr)
|-
|}

Prions cause neurodegenerative disease by aggregating extracellularly within the [[central nervous system]] to form plaques known as [[amyloids]], which disrupt the normal [[tissue (biology)|tissue]] structure. This disruption is characterized by "holes" in the tissue with resultant spongy architecture due to the [[vacuole]] formation in the neurons.<ref name="robspath">{{cite book | veditors = Robbins SL, Cotran RS, Kumar V, Collins T | title = Robbins pathologic basis of disease | publisher = Saunders | location = Philadelphia | year =1999 | isbn = 0-7216-7335-X }}</ref> Other histological changes include [[astrogliosis]] and the absence of an [[inflammation|inflammatory reaction]].<ref name="belay">{{cite journal | vauthors = Belay ED | title = Transmissible spongiform encephalopathies in humans | journal = Annual Review of Microbiology | volume = 53 | pages = 283–314 | year = 1999 | pmid = 10547693 | doi = 10.1146/annurev.micro.53.1.283 | s2cid = 18648029 }}</ref> While the [[incubation period]] for prion diseases is relatively long (5 to 20 years), once symptoms appear the disease progresses rapidly, leading to brain damage and death.<ref name="cdc">{{cite web|url=https://www.cdc.gov/ncidod/dvrd/prions/|title=Prion Diseases|date=2006-01-26|access-date=2010-02-28|publisher=US Centers for Disease Control|archive-url=https://web.archive.org/web/20100304135757/http://www.cdc.gov/ncidod/dvrd/prions/|archive-date=2010-03-04|url-status=dead}}</ref> Neurodegenerative symptoms can include [[convulsion]]s, [[dementia]], [[ataxia]] (balance and coordination dysfunction), and behavioural or personality changes.<ref>{{cite journal | vauthors = Imran M, Mahmood S | title = An overview of human prion diseases | journal = Virology Journal | volume = 8 | issue = 1 | pages = 559 | date = December 2011 | pmid = 22196171 | pmc = 3296552 | doi = 10.1186/1743-422X-8-559 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Mastrianni JA | title = The genetics of prion diseases | journal = Genetics in Medicine | volume = 12 | issue = 4 | pages = 187–195 | date = April 2010 | pmid = 20216075 | doi = 10.1097/GIM.0b013e3181cd7374 | doi-access = free }}</ref>

Many different mammalian species can be affected by prion diseases, as the prion protein (PrP) is very similar in all mammals.<ref>{{cite journal | vauthors = Collinge J | title = Prion diseases of humans and animals: their causes and molecular basis | journal = Annual Review of Neuroscience | volume = 24 | pages = 519–550 | year = 2001 | pmid = 11283320 | doi = 10.1146/annurev.neuro.24.1.519 | url = http://pdfs.semanticscholar.org/650f/8f4c880880d357e5dd82236ba611065e21cc.pdf | url-status = dead | s2cid = 18915904 | archive-url = https://web.archive.org/web/20190225162649/http://pdfs.semanticscholar.org/650f/8f4c880880d357e5dd82236ba611065e21cc.pdf | archive-date = 2019-02-25 }}</ref> Due to small differences in PrP between different species it is unusual for a prion disease to transmit from one species to another. The human prion disease variant Creutzfeldt–Jakob disease, however, is thought to be caused by a prion that typically infects cattle, causing [[bovine spongiform encephalopathy]] and is transmitted through infected meat.<ref name="ironside">{{cite journal | vauthors = Ironside JW | title = Variant Creutzfeldt-Jakob disease: risk of transmission by blood transfusion and blood therapies | journal = Haemophilia | volume = 12 | issue = Suppl 1 | pages = 8–15, discussion 26–28 | date = March 2006 | pmid = 16445812 | doi = 10.1111/j.1365-2516.2006.01195.x | doi-access = free }}</ref>

All known prion diseases are untreatable and fatal.<ref name=":0" /><ref name="gilch">{{cite journal | vauthors = Gilch S, Winklhofer KF, Groschup MH, Nunziante M, Lucassen R, Spielhaupter C, Muranyi W, Riesner D, Tatzelt J, Schätzl HM | title = Intracellular re-routing of prion protein prevents propagation of PrP(Sc) and delays onset of prion disease | journal = The EMBO Journal | volume = 20 | issue = 15 | pages = 3957–66 | date = August 2001 | pmid = 11483499 | pmc = 149175 | doi = 10.1093/emboj/20.15.3957 }}</ref><ref>{{cite journal | vauthors = Agarwal A, Mukhopadhyay S | title = Prion Protein Biology Through the Lens of Liquid-Liquid Phase Separation | journal = Journal of Molecular Biology | volume = 434 | issue = 1 | pages = 167368 | date = January 2022 | pmid = 34808226 | doi = 10.1016/j.jmb.2021.167368 }}</ref>

Until 2015 all known mammalian prion diseases were considered to be caused by the prion protein, [[PRNP|PrP]]; in 2015 [[multiple system atrophy]] was found to be transmissible and was hypothesized to be caused by a new prion, the misfolded form of a protein called [[alpha-synuclein]].<ref name=pmid26324905/> The endogenous, properly folded form of the prion protein is denoted PrP<sup>C</sup> (for '''''C'''ommon'' or '''''C'''ellular''), whereas the disease-linked, misfolded form is denoted PrP<sup>Sc</sup> (for '''''Sc'''rapie''), after one of the diseases first linked to prions and neurodegeneration.<ref name=Krull /><ref name="pmid19242475"/> The precise structure of the prion is not known, though they can be formed spontaneously by combining PrP<sup>C</sup>, homopolymeric polyadenylic acid, and lipids in a [[protein misfolding cyclic amplification]] (PMCA) reaction even in the absence of pre-existing infectious prions.<ref name="Formation of native prions from min"/> This result is further evidence that prion replication does not require genetic information.<ref name="pmid28838669">{{cite journal | vauthors = Moda F | title = Protein Misfolding Cyclic Amplification of Infectious Prions | journal = Progress in Molecular Biology and Translational Science | volume = 150 | pages = 361–374 | date = 2017 | pmid = 28838669 | doi = 10.1016/bs.pmbts.2017.06.016 | isbn = 978-0-12-811226-7 }}</ref>

=== Transmission ===
It has been recognized that prion diseases can arise in three different ways: acquired, familial, or sporadic.<ref>{{cite book | veditors = Groschup MH, Kretzschmar HA | title = Prion Diseases Diagnosis and Pathogeneis | series = Archives of Virology | volume = 16 | location = New York | publisher = Springer | year = 2001 | isbn=978-3-211-83530-2 |doi=10.1007/978-3-7091-6308-5}}</ref> It is often assumed that the diseased form directly interacts with the normal form to make it rearrange its structure. One idea, the "Protein X" hypothesis, is that an as-yet unidentified cellular protein (Protein X) enables the conversion of PrP<sup>C</sup> to PrP<sup>Sc</sup> by bringing a molecule of each of the two together into a complex.<ref>{{cite journal | vauthors = Telling GC, Scott M, Mastrianni J, Gabizon R, Torchia M, Cohen FE, DeArmond SJ, Prusiner SB | title = Prion propagation in mice expressing human and chimeric PrP transgenes implicates the interaction of cellular PrP with another protein | journal = Cell | volume = 83 | issue = 1 | pages = 79–90 | date = October 1995 | pmid = 7553876 | doi = 10.1016/0092-8674(95)90236-8 | s2cid = 15235574 | doi-access = free }}</ref>

The primary method of infection in animals is through ingestion. It is thought that prions may be deposited in the environment through the remains of dead animals and via urine, saliva, and other body fluids. They may then linger in the soil by binding to clay and other minerals.<ref>{{cite journal | vauthors = Johnson CJ, Pedersen JA, Chappell RJ, McKenzie D, Aiken JM | title = Oral transmissibility of prion disease is enhanced by binding to soil particles | journal = PLOS Pathogens | volume = 3 | issue = 7 | pages = e93 | date = July 2007 | pmid = 17616973 | pmc = 1904474 | doi = 10.1371/journal.ppat.0030093 | doi-access = free }}</ref>

A [[University of California]] research team has provided evidence for the theory that infection can occur from prions in manure.<ref>{{cite journal | vauthors = Tamgüney G, Miller MW, Wolfe LL, Sirochman TM, Glidden DV, Palmer C, Lemus A, DeArmond SJ, Prusiner SB | title = Asymptomatic deer excrete infectious prions in faeces | journal = Nature | volume = 461 | issue = 7263 | pages = 529–532 | date = September 2009 | pmid = 19741608 | pmc = 3186440 | doi = 10.1038/nature08289 | bibcode = 2009Natur.461..529T }}</ref> And, since manure is present in many areas surrounding water reservoirs, as well as used on many crop fields, it raises the possibility of widespread transmission. Although it was initially reported in January 2011 that researchers had discovered prions spreading through airborne transmission on [[aerosol]] particles in an [[animal testing]] experiment focusing on [[scrapie]] infection in [[laboratory mice]],<ref name=Haybaeck11>{{cite journal | vauthors = Haybaeck J, Heikenwalder M, Klevenz B, Schwarz P, Margalith I, Bridel C, Mertz K, Zirdum E, Petsch B, Fuchs TJ, Stitz L, Aguzzi A | title = Aerosols transmit prions to immunocompetent and immunodeficient mice | journal = PLOS Pathogens | volume = 7 | issue = 1 | pages = e1001257 | date = January 2011 | pmid = 21249178 | pmc = 3020930 | doi = 10.1371/journal.ppat.1001257 | doi-access = free }}{{Retracted|doi=10.1371/journal.ppat.1012396|pmid=39024193|intentional=yes}}<br />Lay summary: {{cite web | vauthors = Mackenzie D |date=January 13, 2011 |title=Prion disease can spread through air |url=https://www.newscientist.com/article/dn19971-prion-disease-can-spread-through-air |url-access=registration |website=New Scientist}}</ref> this report was retracted in 2024.<ref name=Haybaeck11/> Preliminary evidence supporting the notion that prions can be transmitted through use of urine-derived [[human menopausal gonadotropin]], administered for the treatment of [[infertility]], was published in 2011.<ref name="pmid21448279">{{cite journal | vauthors = Van Dorsselaer A, Carapito C, Delalande F, Schaeffer-Reiss C, Thierse D, Diemer H, McNair DS, Krewski D, Cashman NR | title = Detection of prion protein in urine-derived injectable fertility products by a targeted proteomic approach | journal = PLOS ONE | volume = 6 | issue = 3 | pages = e17815 | date = March 2011 | pmid = 21448279 | pmc = 3063168 | doi = 10.1371/journal.pone.0017815 | doi-access = free | bibcode = 2011PLoSO...617815V }}</ref>

==== Genetic susceptibility ====
The majority of human prion diseases are classified as sporadic Creutzfeldt–Jakob disease (sCJD). Genetic research has identified an association between susceptibility to sCJD and a polymorphism at codon 129 in the PRNP gene, which encodes the prion protein (PrP). A homozygous methionine/methionine (MM) genotype at this position has been shown to significantly increase the risk of developing sCJD when compared to a heterozygous methionine/valine (MV) genotype. Analysis of multiple studies has shown that individuals with the MM genotype are approximately five times more likely to develop sCJD than those with the MV genotype.<ref>{{cite journal |vauthors=Kim YC, Jeong BH |title=The First Meta-Analysis of the M129V Single-Nucleotide Polymorphism (SNP) of the Prion Protein Gene (PRNP) with Sporadic Creutzfeldt-Jakob Disease |journal=Cells |volume=10 |issue=11 |date=November 2021 |page=3132 |pmid=34831353 |pmc=8618741 |doi=10.3390/cells10113132 |doi-access=free}}</ref>

==== Prions in plants ====
In 2015, researchers at [[The University of Texas Health Science Center at Houston]] found that plants can be a vector for prions. When researchers fed hamsters grass that grew on ground where a deer that died with [[chronic wasting disease]] (CWD) was buried, the hamsters became ill with CWD, suggesting that prions can bind to plants, which then take them up into the leaf and stem structure, where they can be eaten by herbivores, thus completing the cycle. It is thus possible that there is a progressively accumulating number of prions in the environment.<ref>{{cite news |vauthors=Beecher C |url=http://www.foodsafetynews.com/2015/06/researchers-make-surprising-discovery-about-spread-of-chronic-wasting-disease/ |title=Surprising' Discovery Made About Chronic Wasting Disease |work=[[Food Safety News]] |date=June 1, 2015 |access-date=2016-04-08 |archive-date=2016-04-28 |archive-url=https://web.archive.org/web/20160428055600/http://www.foodsafetynews.com/2015/06/researchers-make-surprising-discovery-about-spread-of-chronic-wasting-disease/ |url-status=live }}</ref><ref>{{cite journal | vauthors = Pritzkow S, Morales R, Moda F, Khan U, Telling GC, Hoover E, Soto C | title = Grass plants bind, retain, uptake, and transport infectious prions | journal = Cell Reports | volume = 11 | issue = 8 | pages = 1168–75 | date = May 2015 | pmid = 25981035 | pmc = 4449294 | doi = 10.1016/j.celrep.2015.04.036 }}</ref>

=== Sterilization ===
Infectious particles possessing [[nucleic acid]] are dependent upon it to direct their continued replication. Prions, however, are infectious by their effect on normal versions of the protein. Sterilizing prions, therefore, requires the [[denaturation (biochemistry)|denaturation]] of the protein to a state in which the molecule is no longer able to induce the abnormal folding of normal proteins. In general, prions are quite resistant to [[protease]]s, heat, [[ionizing radiation]], and [[formaldehyde]] treatments,<ref>{{cite journal | vauthors = Qin K, O'Donnell M, Zhao RY | title = Doppel: more rival than double to prion | journal = Neuroscience | volume = 141 | issue = 1 | pages = 1–8 | date = August 2006 | pmid = 16781817 | doi = 10.1016/j.neuroscience.2006.04.057 | s2cid = 28822120 }}</ref> although their infectivity can be reduced by such treatments. Effective prion decontamination relies upon protein [[hydrolysis]] or reduction or destruction of [[protein tertiary structure]]. Examples include [[sodium hypochlorite]], [[sodium hydroxide]], and strongly acidic [[detergent]]s such as LpH.<ref>{{cite journal | vauthors = Race RE, Raymond GJ | title = Inactivation of transmissible spongiform encephalopathy (prion) agents by environ LpH | journal = Journal of Virology | volume = 78 | issue = 4 | pages = 2164–5 | date = February 2004 | pmid = 14747583 | pmc = 369477 | doi = 10.1128/JVI.78.4.2164-2165.2004 }}</ref>

The [[World Health Organization]] recommends any of the following three procedures for the sterilization of all heat-resistant surgical instruments to ensure that they are not contaminated with prions:

# Immerse in [[Equivalent concentration|1N]]&nbsp;sodium hydroxide and place in a [[Autoclave#Air removal|gravity-displacement autoclave]] at 121&nbsp;°C for 30&nbsp;minutes; clean; rinse in water; and then perform routine sterilization processes.
# Immerse in 1N&nbsp;sodium hypochlorite (20,000&nbsp;parts per million available chlorine) for 1&nbsp;hour; transfer instruments to water; heat in a gravity-displacement autoclave at 121&nbsp;°C for 1&nbsp;hour; clean; and then perform routine sterilization processes.
# Immerse in 1N&nbsp;sodium hydroxide or sodium hypochlorite (20,000&nbsp;parts per million available chlorine) for 1&nbsp;hour; remove and rinse in water, then transfer to an open pan and heat in a gravity-displacement (121&nbsp;°C) or in a porous-load (134&nbsp;°C) autoclave for 1&nbsp;hour; clean; and then perform routine sterilization processes.<ref>{{cite journal | vauthors = Sutton JM, Dickinson J, Walker JT, Raven ND | title = Methods to minimize the risks of Creutzfeldt-Jakob disease transmission by surgical procedures: where to set the standard? | journal = Clinical Infectious Diseases | volume = 43 | issue = 6 | pages = 757–764 | date = September 2006 | pmid = 16912952 | doi = 10.1086/507030 | doi-access = free }}</ref>

{{convert|134|C}} for 18 minutes in a pressurized steam [[autoclave]] has been found to be somewhat effective in deactivating the agent of disease.<ref>{{cite journal | vauthors = Collins SJ, Lawson VA, Masters CL | title = Transmissible spongiform encephalopathies | journal = Lancet | volume = 363 | issue = 9402 | pages = 51–61 | date = January 2004 | pmid = 14723996 | doi = 10.1016/S0140-6736(03)15171-9 | s2cid = 23212525 }}</ref><ref name="pmid10716712">{{cite journal | vauthors = Brown P, Rau EH, Johnson BK, Bacote AE, Gibbs CJ, Gajdusek DC | title = New studies on the heat resistance of hamster-adapted scrapie agent: threshold survival after ashing at 600 degrees C suggests an inorganic template of replication | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 7 | pages = 3418–21 | date = March 2000 | pmid = 10716712 | pmc = 16254 | doi = 10.1073/pnas.050566797 | doi-access = free | bibcode = 2000PNAS...97.3418B }}</ref> [[Ozone]] sterilization has been studied as a potential method for prion denaturation and deactivation.<ref>{{cite web | url=http://www.hpa.org.uk/hpa/news/articles/press_releases/2005/050414_ozone_sterilizer.htm | title=Ozone Sterilization | date=2005-04-14 | publisher=UK Health Protection Agency | access-date=2010-02-28 |archive-url = https://web.archive.org/web/20070210204514/http://www.hpa.org.uk/hpa/news/articles/press_releases/2005/050414_ozone_sterilizer.htm |archive-date=February 10, 2007 }}</ref> Other approaches being developed include [[thiourea]]-[[urea]] treatment, [[guanidinium chloride]] treatment,<ref>{{cite journal | vauthors = Botsios S, Tittman S, Manuelidis L | title = Rapid chemical decontamination of infectious CJD and scrapie particles parallels treatments known to disrupt microbes and biofilms | journal = Virulence | volume = 6 | issue = 8 | pages = 787–801 | date = 2015 | pmid = 26556670 | pmc = 4826107 | doi = 10.1080/21505594.2015.1098804 }}</ref> and special heat-resistant [[subtilisin]] combined with heat and detergent.<ref>{{cite journal | vauthors = Koga Y, Tanaka S, Sakudo A, Tobiume M, Aranishi M, Hirata A, Takano K, Ikuta K, Kanaya S | title = Proteolysis of abnormal prion protein with a thermostable protease from ''Thermococcus kodakarensis'' KOD1 | journal = Applied Microbiology and Biotechnology | volume = 98 | issue = 5 | pages = 2113–20 | date = March 2014 | pmid = 23880875 | doi = 10.1007/s00253-013-5091-7 | s2cid = 2677641 }}</ref> A number of decontamination reagents have been commercially manufactured with significant differences in efficacy among methods.<ref>{{cite journal |last1=Edgeworth |first1=JA |last2=Sicilia |first2=A |last3=Linehan |first3=J |last4=Brandner |first4=S |last5=Jackson |first5=GS |last6=Collinge |first6=J |title=A standardized comparison of commercially available prion decontamination reagents using the Standard Steel-Binding Assay. |journal=The Journal of General Virology |date=March 2011 |volume=92 |issue=Pt 3 |pages=718–26 |doi=10.1099/vir.0.027201-0 |pmid=21084494 |pmc=3081234}}</ref> A method sufficient for sterilizing prions on one material may fail on another.<ref>{{cite journal | vauthors = Eraña H, Pérez-Castro MÁ, García-Martínez S, Charco JM, López-Moreno R, Díaz-Dominguez CM, Barrio T, González-Miranda E, Castilla J | title = A Novel, Reliable and Highly Versatile Method to Evaluate Different Prion Decontamination Procedures | journal = Frontiers in Bioengineering and Biotechnology | volume = 8 | pages = 589182 | date = 2020 | pmid = 33195153 | pmc = 7658626 | doi = 10.3389/fbioe.2020.589182 | doi-access = free }}</ref>

Renaturation of a completely denatured prion to infectious status has not yet been achieved; however, partially denatured prions can be renatured to an infective status under certain artificial conditions.<ref>{{cite journal | vauthors = Weissmann C, Enari M, Klöhn PC, Rossi D, Flechsig E | title = Transmission of prions | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = s 4 | pages = 16378–83 | date = December 2002 | pmid = 12181490 | pmc = 139897 | doi = 10.1073/pnas.172403799 | doi-access = free | bibcode = 2002PNAS...9916378W }}</ref>

=== Degradation resistance in nature ===
Overwhelming evidence shows that prions resist degradation and persist in the environment for years, and [[protease]]s do not degrade them. Experimental evidence shows that ''unbound'' prions degrade over time, while soil-bound prions remain at stable or increasing levels, suggesting that prions likely accumulate in the environment.<ref>{{cite journal | vauthors = Zabel M, Ortega A | title = The Ecology of Prions | journal = Microbiology and Molecular Biology Reviews | volume = 81 | issue = 3 | date = September 2017 | pmid = 28566466 | pmc = 5584314 | doi = 10.1128/MMBR.00001-17 }}</ref><ref>{{cite journal | vauthors = Kuznetsova A, Cullingham C, McKenzie D, Aiken JM | title = Soil humic acids degrade CWD prions and reduce infectivity | journal = PLOS Pathogens | volume = 14 | issue = 11 | pages = e1007414 | date = November 2018 | pmid = 30496301 | pmc = 6264147 | doi = 10.1371/journal.ppat.1007414 | doi-access = free }}</ref> One 2015 study by US scientists found that repeated drying and wetting may render soil bound prions less infectious, although this was dependent on the soil type they were bound to.<ref>{{cite journal | vauthors = Yuan Q, Eckland T, Telling G, Bartz J, Bartelt-Hunt S | title = Mitigation of prion infectivity and conversion capacity by a simulated natural process--repeated cycles of drying and wetting | journal = PLOS Pathogens | volume = 11 | issue = 2 | pages = e1004638 | date = February 2015 | pmid = 25665187 | pmc = 4335458 | doi = 10.1371/journal.ppat.1004638 | doi-access = free }}</ref>

=== Degradation by living beings ===
More recent studies suggest scrapie prions can be degraded by diverse cellular machinery of the affected animal cell. In an infected cell, extracellular lysosomal PrP<sup>Sc</sup> does not tend to accumulate and is rapidly cleared by the [[lysosome]] via the [[endosome]]. The intracellular portion is harder to clear and tends to build up. The [[Proteasome|ubiquitin proteasome system]] appears to be able to degrade small enough aggregates. [[Autophagy]] plays a bigger role by accepting PrP<sup>Sc</sup> from the ER lumen and degrading it. Altogether these mechanisms allow the cell to delay its death from being overwhelmed by misfolded proteins.<ref name=":1" /> Inhibition of autophagy accelerates prion accumulation whereas encouragement of autophagy promotes prion clearance. Some autophagy-promoting compounds have shown promise in animal models by delaying disease onset and death.<ref name=":1">{{cite journal | vauthors = López-Pérez Ó, Badiola JJ, Bolea R, Ferrer I, Llorens F, Martín-Burriel I | title = An Update on Autophagy in Prion Diseases | language = English | journal = Frontiers in Bioengineering and Biotechnology | volume = 8 | pages = 975 | date = 2020-08-27 | pmid = 32984276 | pmc = 7481332 | doi = 10.3389/fbioe.2020.00975 | doi-access = free }}</ref>

In addition, [[keratinase]] from [[Bacillus licheniformis|''B. licheniformis'']],<ref>{{cite journal | vauthors = Langeveld JP, Wang JJ, Van de Wiel DF, Shih GC, Garssen GJ, Bossers A, Shih JC | title = Enzymatic degradation of prion protein in brain stem from infected cattle and sheep | journal = The Journal of Infectious Diseases | volume = 188 | issue = 11 | pages = 1782–9 | date = December 2003 | pmid = 14639552 | doi = 10.1086/379664 }}</ref><ref>{{cite journal | vauthors = Okoroma EA, Purchase D, Garelick H, Morris R, Neale MH, Windl O, Abiola OO | title = Enzymatic formulation capable of degrading scrapie prion under mild digestion conditions | journal = PLOS ONE | volume = 8 | issue = 7 | pages = e68099 | date = 2013-07-16 | pmid = 23874511 | pmc = 3712960 | doi = 10.1371/journal.pone.0068099 | doi-access = free | bibcode = 2013PLoSO...868099O }}</ref> alkaline [[serine protease]] from ''Streptomyces sp'',<ref>{{cite journal | vauthors = Hui Z, Doi H, Kanouchi H, Matsuura Y, Mohri S, Nonomura Y, Oka T | title = Alkaline serine protease produced by Streptomyces sp. degrades PrP(Sc) | journal = Biochemical and Biophysical Research Communications | volume = 321 | issue = 1 | pages = 45–50 | date = August 2004 | pmid = 15358213 | doi = 10.1016/j.bbrc.2004.06.100 }}</ref> [[subtilisin]]-like pernisine from ''[[Aeropyrum pernix]]'',<ref>{{cite journal | vauthors = Snajder M, Vilfan T, Cernilec M, Rupreht R, Popović M, Juntes P, Serbec VČ, Ulrih NP | title = Enzymatic degradation of PrPSc by a protease secreted from Aeropyrum pernix K1 | journal = PLOS ONE | volume = 7 | issue = 6 | pages = e39548 | date = 2012 | pmid = 22761822 | pmc = 3386259 | doi = 10.1371/journal.pone.0039548 | doi-access = free | bibcode = 2012PLoSO...739548S }}</ref> alkaline protease from ''[[Nocardiopsis]] sp'',<ref>{{cite journal | vauthors = Mitsuiki S, Hui Z, Matsumoto D, Sakai M, Moriyama Y, Furukawa K, Kanouchi H, Oka T | title = Degradation of PrP(Sc) by keratinolytic protease from Nocardiopsis sp. TOA-1 | journal = Bioscience, Biotechnology, and Biochemistry | volume = 70 | issue = 5 | pages = 1246–8 | date = May 2006 | pmid = 16717429 | doi = 10.1271/bbb.70.1246 }}</ref> [[nattokinase]] from ''[[Bacillus subtilis|B. subtilis]]'',<ref>{{cite journal | vauthors = Hsu RL, Lee KT, Wang JH, Lee LY, Chen RP | title = Amyloid-degrading ability of nattokinase from Bacillus subtilis natto | journal = Journal of Agricultural and Food Chemistry | volume = 57 | issue = 2 | pages = 503–8 | date = January 2009 | pmid = 19117402 | doi = 10.1021/jf803072r | bibcode = 2009JAFC...57..503H }}</ref> engineered subtilisins from ''B. lentus''<ref>{{Cite journal | vauthors = Booth CJ, Johnson CJ, Pedersen JA |date= April 2013 |title=Microbial and enzymatic inactivation of prions in soil environments |url=https://linkinghub.elsevier.com/retrieve/pii/S0038071713000035 |journal=Soil Biology and Biochemistry |volume=59 |pages=1–15 |doi=10.1016/j.soilbio.2012.12.016 |bibcode=2013SBiBi..59....1B |issn=0038-0717}}</ref><ref>{{cite journal | vauthors = Dickinson J, Murdoch H, Dennis MJ, Hall GA, Bott R, Crabb WD, Penet C, Sutton JM, Raven ND | title = Decontamination of prion protein (BSE301V) using a genetically engineered protease | journal = The Journal of Hospital Infection | volume = 72 | issue = 1 | pages = 65–70 | date = May 2009 | pmid = 19201054 | doi = 10.1016/j.jhin.2008.12.007 }}</ref> and serine protease from three lichen species<ref>{{cite journal | vauthors = Johnson CJ, Bennett JP, Biro SM, Duque-Velasquez JC, Rodriguez CM, Bessen RA, Rocke TE | title = Degradation of the disease-associated prion protein by a serine protease from lichens | journal = PLOS ONE | volume = 6 | issue = 5 | pages = e19836 | date = May 2011 | pmid = 21589935 | pmc = 3092769 | doi = 10.1371/journal.pone.0019836 | doi-access = free | bibcode = 2011PLoSO...619836J }}</ref> have been found to degrade PrP<sup>Sc</sup>.