Prion
Prion | |
---|---|
3D structure of major prion protein | |
Pronunciation | |
Specialty | Infectious diseases |
A prion
The word prion is derived from the term "proteinaceous infectious particle"., or both).
Most prions are twisted isoforms of the major prion protein (PrP), a natural protein whose normal function is uncertain. They are hypothesized as the cause of transmissible spongiform encephalopathies (TSEs),[8] including scrapie in sheep, chronic wasting disease (CWD) in deer, bovine spongiform encephalopathy (BSE) in cattle (mad cow disease), feline spongiform encephalopathy (FSE) in felines, and Creutzfeldt–Jakob disease (CJD) and fatal insomnia in humans.
All known prion diseases in mammals affect the structure of the brain or other neural tissue; all are progressive, have no known effective treatment, and are always fatal.[9] All known mammalian prion diseases were caused by PrP until 2015, when a prion form of alpha-synuclein was hypothesized to cause multiple system atrophy (MSA).[10]
Prions are a type of
A prion disease is a type of
Prion aggregates are stable, and this structural stability means that prions are resistant to denaturation by chemical and physical agents: they cannot be destroyed by ordinary disinfection or cooking. This makes disposal and containment of these particles difficult, and the risk of iatrogenic spread through medical instruments a growing concern.
Etymology and pronunciation
The word prion, coined in 1982 by Stanley B. Prusiner, is derived from protein and infection, hence prion,[24] and is short for "proteinaceous infectious particle",[10] in reference to its ability to self-propagate and transmit its conformation to other proteins.[25] Its main pronunciation is /ˈpriːɒn/ ⓘ,[26][27][28] although /ˈpraɪɒn/, as the homographic name of the bird (prions or whalebirds) is pronounced,[28] is also heard.[29] In his 1982 paper introducing the term, Prusiner specified that it is "pronounced pree-on".[24]
Prion protein
Structure
The major prion protein (PrP) that prions are made of is found throughout the body, even in healthy people and animals. However, PrP found in infectious material has a different structure and is resistant to proteases, the enzymes in the body that can normally break down proteins. The normal form of the protein is called PrPC, while the infectious form is called PrPSc – the C refers to 'cellular' PrP, while the Sc refers to 'scrapie', the prototypic prion disease, occurring in sheep.[30] PrP can also be induced to fold into other more-or-less well-defined isoforms in vitro; although their relationships to the form(s) that are pathogenic in vivo is often unclear, high-resolution structural analyses have begun to reveal structural features that correlate with prion infectivity.[31]
PrPC
PrPC is a normal protein found on the
PrPres
Protease-resistant PrPSc-like protein (PrPres) is the name given to any isoform of PrPc which is structurally altered and converted into a misfolded proteinase K-resistant form.[40] To model conversion of PrPC to PrPSc in vitro, Kocisko et al. showed that PrPSc could cause PrPC to convert to PrPres under cell-free conditions [41] and Soto et al. demonstrated sustained amplification of PrPres and prion infectivity by a procedure involving cyclic amplification of protein misfolding.[42] The term "PrPres" may refer either to protease-resistant forms of PrPSc, which is isolated from infectious tissue and associated with the transmissible spongiform encephalopathy agent, or to other protease-resistant forms of PrP that, for example, might be generated in vitro.[43] Accordingly, unlike PrPSc, PrPres may not necessarily be infectious.
PrPSc
The infectious
Normal function of PrP
The physiological function of the prion protein remains poorly understood. While data from in vitro experiments suggest many dissimilar roles, studies on PrP
PrP and regulated cell death
MAVS, RIP1, and RIP3 are prion-like proteins found in other parts of the body. They also polymerise into filamentous amyloid fibers which initiate regulated cell death in the case of a viral infection to prevent the spread of virions to other, surrounding cells.[60]
PrP and long-term memory
A review of evidence in 2005 suggested that PrP may have a normal function in maintenance of long-term memory.[61] As well, a 2004 study found that mice lacking genes for normal cellular PrP protein show altered hippocampal long-term potentiation.[62][63] A recent study that also suggests why this might be the case, found that neuronal protein CPEB has a similar genetic sequence to yeast prion proteins. The prion-like formation of CPEB is essential for maintaining long-term synaptic changes associated with long-term memory formation.[64]
PrP and stem cell renewal
A 2006 article from the Whitehead Institute for Biomedical Research indicates that PrP expression on stem cells is necessary for an organism's self-renewal of bone marrow. The study showed that all long-term hematopoietic stem cells express PrP on their cell membrane and that hematopoietic tissues with PrP-null stem cells exhibit increased sensitivity to cell depletion.[65]
PrP and innate immunity
There is some evidence that PrP may play a role in
Replication
The first hypothesis that tried to explain how prions replicate in a protein-only manner was the heterodimer model.[67] This model assumed that a single PrPSc molecule binds to a single PrPC molecule and catalyzes its conversion into PrPSc. The two PrPSc molecules then come apart and can go on to convert more PrPC. However, a model of prion replication must explain both how prions propagate, and why their spontaneous appearance is so rare. Manfred Eigen showed that the heterodimer model requires PrPSc to be an extraordinarily effective catalyst, increasing the rate of the conversion reaction by a factor of around 1015.[68] This problem does not arise if PrPSc exists only in aggregated forms such as amyloid, where cooperativity may act as a barrier to spontaneous conversion. What is more, despite considerable effort, infectious monomeric PrPSc has never been isolated.[citation needed]
An alternative model assumes that PrPSc exists only as
The mechanism of prion replication has implications for designing drugs. Since the incubation period of prion diseases is so long, an effective drug does not need to eliminate all prions, but simply needs to slow down the rate of exponential growth. Models predict that the most effective way to achieve this, using a drug with the lowest possible dose, is to find a drug that binds to fibril ends and blocks them from growing any further.[75]
Researchers at Dartmouth College discovered that endogenous host cofactor molecules such as the phospholipid molecule (e.g. phosphatidylethanolamine) and
Transmissible spongiform encephalopathies
Affected animal(s) | Disease |
---|---|
Sheep, Goat
|
Scrapie[78] |
Cattle | Bovine spongiform encephalopathy[78] |
Camel[79] | Camel spongiform encephalopathy (CSE) |
Mink[78] | Transmissible mink encephalopathy (TME) |
White-tailed deer, elk, mule deer, moose[78] | Chronic wasting disease (CWD) |
Cat[78] | Feline spongiform encephalopathy (FSE) |
Greater Kudu[78]
|
Exotic ungulate encephalopathy (EUE) |
Ostrich[80] | Spongiform encephalopathy (unknown if transmissible) |
Human | Creutzfeldt–Jakob disease (CJD)[78] |
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)[78] | |
Fatal insomnia (FFI)[81] | |
Kuru[78] | |
Familial spongiform encephalopathy[82] | |
Variably protease-sensitive prionopathy (VPSPr) |
Prions cause neurodegenerative disease by aggregating extracellularly within the
Many different mammalian species can be affected by prion diseases, as the prion protein (PrP) is very similar in all mammals.[86] 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.[87]
All known prion diseases are untreatable and fatal.[medical citation needed][88]
Until 2015 all known mammalian prion diseases were considered to be caused by the prion protein,
Transmission
It has been recognized that prion diseases can arise in three different ways: acquired, familial, or sporadic.[90] 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 PrPC to PrPSc by bringing a molecule of each of the two together into a complex.[91]
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.[92]
A
Prions in plants
In 2015, researchers at
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 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 proteases, heat, ionizing radiation, and formaldehyde treatments,[98] 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 detergents such as LpH.[99]
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 1N sodium hydroxide and place in a gravity-displacement autoclave at 121 °C for 30 minutes; clean; rinse in water; and then perform routine sterilization processes.
- Immerse in 1N sodium hypochlorite (20,000 parts per million available chlorine) for 1 hour; transfer instruments to water; heat in a gravity-displacement autoclave at 121 °C for 1 hour; clean; and then perform routine sterilization processes.
- Immerse in 1N sodium hydroxide or sodium hypochlorite (20,000 parts per million available chlorine) for 1 hour; remove and rinse in water, then transfer to an open pan and heat in a gravity-displacement (121 °C) or in a porous-load (134 °C) autoclave for 1 hour; clean; and then perform routine sterilization processes.[100]
134 °C (273 °F) for 18 minutes in a pressurized steam autoclave has been found to be somewhat effective in deactivating the agent of disease.[101][102] Ozone sterilization is currently being studied as a potential method for prion denaturation and deactivation.[103] Other approaches being developed include thiourea-urea treatment, guanidinium chloride treatment,[104] and special heat-resistant subtilisin combined with heat and detergent.[105] A method sufficient for sterilizing prions on one material may fail on another.[106]
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.[107]
Degradation resistance in nature
Overwhelming evidence shows that prions resist degradation and persist in the environment for years, and proteases 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.[108][109] 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.[110]
Fungi
Proteins showing prion-type behavior are also found in some fungi, which has been useful in helping to understand mammalian prions. Fungal prions do not always cause disease in their hosts.[111] In yeast, protein refolding to the prion configuration is assisted by chaperone proteins such as Hsp104.[21] All known prions induce the formation of an amyloid fold, in which the protein polymerises into an aggregate consisting of tightly packed beta sheets. Amyloid aggregates are fibrils, growing at their ends, and replicate when breakage causes two growing ends to become four growing ends. The incubation period of prion diseases is determined by the exponential growth rate associated with prion replication, which is a balance between the linear growth and the breakage of aggregates.[73]
Fungal proteins exhibiting templated conformational change[
Research into fungal prions has given strong support to the protein-only concept, since purified protein extracted from cells with a prion state has been demonstrated to convert the normal form of the protein into a misfolded form in vitro, and in the process, preserve the information corresponding to different strains of the prion state. It has also shed some light on prion domains, which are regions in a protein that promote the conversion into a prion. Fungal prions have helped to suggest mechanisms of conversion that may apply to all prions, though fungal prions appear distinct from infectious mammalian prions in the lack of cofactor required for propagation. The characteristic prion domains may vary between species – e.g., characteristic fungal prion domains are not found in mammalian prions.[citation needed]
Protein | Natural host | Normal function | Prion state | Prion phenotype | Year identified |
---|---|---|---|---|---|
Ure2p | Saccharomyces cerevisiae | Nitrogen catabolite repressor | [URE3] | Growth on poor nitrogen sources | 1994 |
Sup35p | S. cerevisiae | Translation termination factor | [PSI+] | Increased levels of nonsense suppression | 1994 |
HET-S | Podospora anserina | Regulates heterokaryon incompatibility | [Het-s] | Heterokaryon formation between incompatible strains | |
Rnq1p | S. cerevisiae | Protein template factor | [RNQ+], [PIN+] | Promotes aggregation of other prions | |
Swi1 | S. cerevisiae | Chromatin remodeling | [SWI+] | Poor growth on some carbon sources | 2008 |
Cyc8 | S. cerevisiae | Transcriptional repressor | [OCT+] | Transcriptional derepression of multiple genes | 2009 |
Mot3 | S. cerevisiae | Nuclear transcription factor | [MOT3+] | Transcriptional derepression of anaerobic genes | 2009 |
Sfp1 | S. cerevisiae | Putative transcription factor | [ISP+] | Antisuppression | 2010[116][contradictory] |
Treatments
There are no effective treatments for prion diseases.[117] Clinical trials in humans have not met with success and have been hampered by the rarity of prion diseases.[117] Although some potential treatments have shown promise in the laboratory, none have been effective once the disease has commenced.[118]
In other diseases
Prion-like domains have been found in a variety of other mammalian proteins. Some of these proteins have been implicated in the ontogeny of age-related neurodegenerative disorders such as
The definition of a prion-like domain arises from the study of fungal prions. In yeast, prionogenic proteins have a portable prion domain that is both necessary and sufficient for self-templating and protein aggregation. This has been shown by attaching the prion domain to a reporter protein, which then aggregates like a known prion. Similarly, removing the prion domain from a fungal prion protein inhibits prionogenesis. This modular view of prion behaviour has led to the hypothesis that similar prion domains are present in animal proteins, in addition to PrP.[119] These fungal prion domains have several characteristic sequence features. They are typically enriched in asparagine, glutamine, tyrosine and glycine residues, with an asparagine bias being particularly conducive to the aggregative property of prions. Historically, prionogenesis has been seen as independent of sequence and only dependent on relative residue content. However, this has been shown to be false, with the spacing of prolines and charged residues having been shown to be critical in amyloid formation.[20]
Bioinformatic screens have predicted that over 250 human proteins contain prion-like domains (PrLD). These domains are hypothesized to have the same transmissible, amyloidogenic properties of PrP and known fungal proteins. As in yeast, proteins involved in gene expression and RNA binding seem to be particularly enriched in PrLD's, compared to other classes of protein. In particular, 29 of the known 210 proteins with an RNA recognition motif also have a putative prion domain. Meanwhile, several of these RNA-binding proteins have been independently identified as pathogenic in cases of ALS, FTLD-U, Alzheimer's disease, and Huntington's disease.[122]
Role in neurodegenerative disease
The pathogenicity of prions and proteins with prion-like domains is hypothesized to arise from their self-templating ability and the resulting exponential growth of amyloid fibrils. The presence of amyloid fibrils in patients with degenerative diseases has been well documented. These amyloid fibrils are seen as the result of pathogenic proteins that self-propagate and form highly stable, non-functional aggregates.[122] While this does not necessarily imply a causal relationship between amyloid and degenerative diseases, the toxicity of certain amyloid forms and the overproduction of amyloid in familial cases of degenerative disorders supports the idea that amyloid formation is generally toxic.[123]
Specifically, aggregation of
Similarly, pathogenic mutations have been identified in the prion-like domains of heterogeneous nuclear riboproteins hnRNPA2B1 and hnRNPA1 in familial cases of muscle, brain, bone and motor neuron degeneration. The wild-type form of all of these proteins show a tendency to self-assemble into amyloid fibrils, while the pathogenic mutations exacerbate this behaviour and lead to excess accumulation.[124]
Weaponization
Prions could theoretically be employed as a weaponized agent.[125][126] With potential fatality rates of 100%, prions could be an effective bioweapon, sometimes called a "biochemical weapon", because a prion is a biochemical. An unfavorable aspect is prions' very long incubation periods. Persistent heavy exposure of prions to the intestine might shorten the overall onset.[127] Another aspect of using prions in warfare is the difficulty of detection and decontamination.[128]
History
In the 18th and 19th centuries, exportation of sheep from Spain was observed to coincide with a disease called scrapie. This disease caused the affected animals to "lie down, bite at their feet and legs, rub their backs against posts, fail to thrive, stop feeding and finally become lame".[129] The disease was also observed to have the long incubation period that is a key characteristic of transmissible spongiform encephalopathies (TSEs). Although the cause of scrapie was not known back then, it is probably the first transmissible spongiform encephalopathy to be recorded.[130]
In the 1950s,
In the first hypothesis, he suggested that if the protein is the product of a normally suppressed gene, and introducing the protein could induce the gene's expression, that is, wake the dormant gene up, then the result would be a process indistinguishable from replication, as the gene's expression would produce the protein, which would then wake the gene in other cells.[citation needed]
His second hypothesis forms the basis of the modern prion theory, and proposed that an abnormal form of a cellular protein can convert normal proteins of the same type into its abnormal form, thus leading to replication.[citation needed]
His third hypothesis proposed that the agent could be an antibody if the antibody was its own target antigen, as such an antibody would result in more and more antibody being produced against itself. However, Griffith acknowledged that this third hypothesis was unlikely to be true due to the lack of a detectable immune response.[137]
In 1982, Stanley B. Prusiner of the University of California, San Francisco, announced that his team had purified the hypothetical infectious protein, which did not appear to be present in healthy hosts, though they did not manage to isolate the protein until two years after Prusiner's announcement.[140][24] The protein was named a prion, for "proteinacious infectious particle", derived from the words protein and infection. When the prion was discovered, Griffith's first hypothesis, that the protein was the product of a normally silent gene was favored by many. It was subsequently discovered, however, that the same protein exists in normal hosts but in different form.[141]
Following the discovery of the same protein in different form in uninfected individuals, the specific protein that the prion was composed of was named the prion protein (PrP), and Griffith's second hypothesis that an abnormal form of a host protein can convert other proteins of the same type into its abnormal form, became the dominant theory.[137] Prusiner was awarded the Nobel Prize in Physiology or Medicine in 1997 for his research into prions.[142][143]
See also
- Bovine spongiform encephalopathy (BSE)
- Diseases of abnormal polymerization
- Mad cow crisis
- Prion pseudoknot
- Subviral agents
- Tau protein
References
- ^ "English pronunciation of prion". Cambridge Dictionary. Cambridge University Press. Archived from the original on April 24, 2017. Retrieved March 30, 2020.
- ^ "Definition of Prion". Dictionary.com. Random House, Inc. 2021. Definition 2 of 2. Archived from the original on September 12, 2021. Retrieved September 12, 2021.
- ^ "Transmissible Spongiform Encephalopathies". National Institute of Neurological Disorders and Stroke. Retrieved April 23, 2023.
- ^ "Prion diseases". Diseases and conditions. National Institute of Health. Archived from the original on May 22, 2020. Retrieved June 20, 2018.
- ^ Kumar V (2021). Robbins & Cotran Pathologic Basis of Disease (10th ed.).
- ^ "What Is a Prion?". Scientific American. Archived from the original on May 16, 2018. Retrieved May 15, 2018.
- ^ "Prion infectious agent". Encyclopaedia Britannica. Archived from the original on May 16, 2018. Retrieved May 15, 2018.
- S2CID 22417182.
- PMID 9811807.
- ^ PMID 26324905.. Scientific American.
Lay summary: Makin S (September 1, 2015). "A Red Flag for a Neurodegenerative Disease That May Be Transmissible" - ^ a b Brahic M (November 10, 2021). "The surprising upsides of the prions behind horrifying brain diseases". New Scientist. Archived from the original on November 13, 2021. Retrieved November 13, 2021.
- PMID 11260793.
- PMID 23635781.
- PMID 18368143.
- ^ "Prion diseases". United States Centers for Disease Control and Prevention. May 3, 2019. Archived from the original on May 18, 2020. Retrieved September 8, 2017.
- ^ PMID 19242475.
- ^ S2CID 38287298.
- ^ S2CID 206558562.
- PMID 25792864.
- ^ PMID 19345193.
- ^ PMID 18172195.
- S2CID 3060439.
- . BBC News. January 1, 2010.
- ^ S2CID 7447120. Archived from the original(PDF) on July 20, 2020.
- ^ "Stanley B. Prusiner – Autobiography". NobelPrize.org. Archived from the original on June 16, 2013. Retrieved January 2, 2007.
- PMID 22607731.
- ^ "Dorland's Illustrated Medical Dictionary". Elsevier. Archived from the original on January 11, 2014. Retrieved July 22, 2016.
- ^ a b "Merriam-Webster's Unabridged Dictionary". Merriam-Webster. Archived from the original on May 25, 2020. Retrieved July 22, 2016.
- ^ "The American Heritage Dictionary of the English Language". Houghton Mifflin Harcourt. Archived from the original on September 25, 2015. Retrieved July 22, 2016.
- from the original on July 28, 2020. Retrieved July 28, 2020.
- PMID 35752366.
- S2CID 34141310.
- S2CID 39791520.
- PMID 9391046.
- S2CID 20176119. Archived from the original(PDF) on February 23, 2019.
- ^ ISBN 978-0-8247-4083-2. Archivedfrom the original on August 20, 2020. Retrieved June 2, 2020.
- S2CID 4388803.
- S2CID 20992257.
- PMID 19278297.
- PMID 14522846.
- S2CID 4337709.
- S2CID 4317585.
- PMID 15297610.
- PMID 1678278.
- PMID 8104185.
- PMID 7902575.
- PMID 34433091.
- PMID 35831291.
- PMID 35831275.
- PMID 35819518.
- PMID 11891310.
- PMID 34433091.
- S2CID 4355092.
- PMID 8953038.
- S2CID 6031488.
- PMID 36342968.
- PMID 36646960.
- PMID 26809254.
- S2CID 84980140.
- PMID 30050058.
- S2CID 5575951.
- PMID 15530652.
- PMID 23407955.
- PMID 27726526.
- PMID 16467153.
- PMID 30480243.
- PMID 7909169.
- PMID 8981746.
- PMID 1684986.
- S2CID 13098083.
- PMID 8760444.
- PMID 9246476.
- ^ PMID 10326247.
- S2CID 6267152.
- PMID 11152275.
- ^ PMID 17535913.
- PMID 22711839.
- ^ a b c d e f g h i "90. Prions". ICTVdB Index of Viruses. U.S. National Institutes of Health website. February 14, 2002. Archived from the original on August 27, 2009. Retrieved February 28, 2010.
- PMID 29652245.
- ^ Hussein MF, Al-Mufarrej SI (2004). "Prion Diseases: A Review; II. Prion Diseases in Man and Animals" (PDF). Scientific Journal of King Faisal University (Basic and Applied Sciences). 5 (2): 139. Archived (PDF) from the original on April 21, 2016. Retrieved April 9, 2016.
- . BBC News. May 28, 1999.
- S2CID 22600579.
- ISBN 072167335X.
- S2CID 18648029.
- ^ "Prion Diseases". US Centers for Disease Control. January 26, 2006. Archived from the original on March 4, 2010. Retrieved February 28, 2010.
- S2CID 18915904. Archived from the original(PDF) on February 25, 2019.
- PMID 16445812.
- PMID 11483499.
- PMID 28838669.
- ISBN 978-3-211-83530-2.
- S2CID 15235574.
- PMID 17616973.
- PMID 19741608.
- . New Scientist.
- PMID 21448279.
- ^ Beecher C (June 1, 2015). "Surprising' Discovery Made About Chronic Wasting Disease". Food Safety News. Archived from the original on April 28, 2016. Retrieved April 8, 2016.
- PMID 25981035.
- S2CID 28822120.
- PMID 14747583.
- PMID 16912952.
- S2CID 23212525.
- PMID 10716712.
- ^ "Ozone Sterilization". UK Health Protection Agency. April 14, 2005. Archived from the original on February 10, 2007. Retrieved February 28, 2010.
- PMID 26556670.
- S2CID 2677641.
- PMID 33195153.
- PMID 12181490.
- PMID 28566466.
- PMID 30496301.
- PMID 25665187.
- PMID 11260797.
- PMID 17893150.
- PMID 23485338.
- S2CID 206527151.
- PMID 22337056.
- PMID 20498075.
- ^ (PDF) from the original on March 12, 2020. Retrieved March 5, 2020.
- ^ "Prion Clinic – Drug treatments". September 13, 2017. Archived from the original on January 29, 2020. Retrieved January 29, 2020.
- ^ PMID 22445064.
- PMID 24280941.
- PMID 24005412.
- ^ PMID 22424229.
- S2CID 211728879.
- PMID 23455423.
- ^ "What are Biological Weapons?". United Nations, Office for Disarmament Affairs. Archived from the original on May 21, 2021. Retrieved May 21, 2021.
- ^ "Prions: the danger of biochemical weapons" (PDF). Archived (PDF) from the original on December 9, 2020. Retrieved May 21, 2021.
- ^ "The Next Plague: Prions are Tiny, Mysterious and Frightening". American Council on Science and Health. March 20, 2017. Archived from the original on May 21, 2021. Retrieved May 21, 2021.
- ^ "Prions as Bioweapons? - Much Ado About Nothing; or Apt Concerns Over Tiny Proteins used in Biowarfare". Defence iQ. September 13, 2019. Archived from the original on May 21, 2021. Retrieved May 21, 2021.
- ^ "How Prions Came to Be: A Brief History – Infectious Disease: Superbugs, Science, & Society". Archived from the original on September 17, 2021. Retrieved September 17, 2021.
- PMID 36654484.
- S2CID 4195902.
- S2CID 4171947.
- PMID 5950508.
- PMID 4175093.
- S2CID 4195610.
- S2CID 4171947.
- ^ ISBN 978-0-203-91297-3. Archivedfrom the original on March 22, 2022. Retrieved July 27, 2018 – via ResearchGate.
- S2CID 4164029.
- PMID 27482900.
- ^ Taubes G (December 1986). "The game of name is fame. But is it science?". Discover. 7 (12): 28–41.
- PMID 26645475.
- ^ "The Nobel Prize in Physiology or Medicine, 1997". NobelPrize.org. Archived from the original on August 9, 2018. Retrieved February 28, 2010.
The Nobel Prize in Physiology or Medicine 1997 was awarded to Stanley B. Prusiner 'for his discovery of Prions - a new biological principle of infection.'
- ^ Frazer J. "Prions Are Forever". Scientific American Blog Network. Archived from the original on January 4, 2022. Retrieved December 28, 2021.
External links
- CDC – US Center for Disease Control and Prevention – information on prion diseases
- World Health Organisation – WHO information on prion diseases
- The UK BSE Inquiry – Report of the UK public inquiry into BSE and variant CJD
- UK Spongiform Encephalopathy Advisory Committee (SEAC)