Detergents alter proteinase K resistance of PrPSc in various transmissible spongiform encephalopathies (TSEs) (2023)

article preview

  • Abstract
  • to introduce
  • partial excerpt
  • References (32)
  • Quoted by (15)
  • Featured Articles (6)

Veterinary Microbiology

Volume 157, issues 1-2,

25 maja 2012 r

, s. 23-31

The author link opens the overlay panel,,,,,,,,


Prion diseases are detected by detecting their proteinase K resistant prion protein fragment (PrPscienceDifferent biochemical protocols use different detergents for tissue preparation. We found resistance to PrPscienceProteinase K inhibition can vary greatly depending on the detergent used. In our study, we compared the most commonly used detergents with eight different onesTokyo Stock ExchangeReagents from different species and different forms of prion diseases. For high throughput, we use membrane adsorption tests to detect small amounts of prion aggregates andWestern blot.Using DOC,SLS,Safety Data Sheetor different concentrations of Triton X-100, were digested with different amounts of proteinase K. Detergents may increase or decrease the detection of PrPscienceAfter digestion with proteinase K. The detection of PrP depends on the type of detergent and its concentration - but also on the species of the TSE-producing host and the form of the disease or the type of prion -sciencecan be very different. The results obtained here may contribute to the development or improvement of PrPscienceDetection methods that indicate the action of the detergent, which can additionally be used to remove stains. A likely explanation for the detergent effects described in this paper may be PrP-related lipid interactionsscienceThis can stabilize the aggregates.

to introduce

Chronic wasting disease (CWD) in deer, scrapie in sheep and goats, bovine spongiform encephalopathy (BSE) in cattle and Creutzfeldt-Jakob disease (CJD) in humans are lethal transmissible spongiform encephalopathy (TSE), also known as prion disease. These neurodegenerative diseases are characterized by detectable aggregates of partially protease-resistant, self-replicating proteins called "infectious protein particles" (hereinafter referred to as "prions") in the central nervous system (CNS). According to the prion hypothesis, the disease-associated prion protein (PrPscience) is the main or only component of the infectious agent (Prusiner, 1982). Prion infectivity, aggregation of prion proteins and PrPscienceappear to be closely related (Beekes et al., 1996; Prusiner et al., 1983). Physiological isoform, cell surface protein (PrP).C), expressed not only in the central nervous system, but also in many extracerebral tissues. These two isoforms share the same amino acid sequence, three glycosylation forms, and a lipid anchor, but differ in protein conformation. It reflects conformational differences, e.g. through the insolubility of aggregated PrPsciencein aqueous buffers and their propensity to form fibrils (Meyer et al., 1986). Proteinase K (pK) Digestion of PrPscienceN-terminal shortening to amino acids 82 or 97 in human CJD (Parchi et al., 2000), amino acids 81-89 in scrapie, amino acids 96-97 in classic BSE (Hayashi et al., 2005) and CWD Amino acids 82 and 78w (Xie et al., 2006). Detection of the proteinase K resistant form of PrPscienceUse as a diagnostic tool and marker for prion diseases (Bolton et al., 1982). Partial resistance of PrP to proteasesscienceIt has been widely accepted as the biochemical basis for distinguishing PrPCi PrPscienceMany factors can influence this, such as the interaction time of the enzyme and PrPscience, enzyme concentration (McKinley et al., 1983) or the addition of chemicals: urea, GdnSCN and detergents such as sodium dodecyl sulfate (SDS), reduce the resistance of PrP to proteinase Kscience(Madec et al., 1997, Oesch et al., 1994). Chaotropic salts destabilize proteins by breaking hydrogen bonds, while detergents affect the tertiary structure of proteins by interacting with both hydrophilic and hydrophobic regions of the molecule (Hörnlimann et al., 2007). Detergents are commonly used in tissue homogenates and pK digestion buffers. The concentrations and combinations of detergents vary greatly. It is further known that PrPscienceSome TSE aggregates are more resistant to proteinase K digestion than others (Kuczius and Groschup, 1999). This can cause problems when diagnostic methods are not suitable for detecting prion diseases where resistance to proteases is relatively low. Unlike PrPscienceClassic scrapie, PrPscienceThe number of atypical scrapie/Nor98 was completely reduced when thorough pK digestion was performed (Buschmann et al., 2004; Everest et al., 2006; Klingeborn et al., 2006). This is one of the reasons why atypical/Nor98 scrapie was identified as sheep scrapie only a few years ago (Benestad et al., 2003). Classic scrapie and chronic wasting disease share many features, such as the neuropathology of PrPscienceDeposition patterns and horizontal transport rates (Williams, 2003). CWD has been recognized as a disease entity, but differences in the transmission of CWD to rodents have been noted in different susceptible species. These findings suggest the presence of strains known to be associated with other TSEs such as classical scrapie (Sigurdson, 2008, Williams, 2005). The effect of certain detergents on PrP stability was evident in the CWD study in elk and white-tailed deerscienceThe effect on proteinase K has not been systematically investigated. Therefore, our approach was to investigate the effect of different detergents in the homogenization buffer on PrP resistancescienceAgainst pK digestion under typical routine conditions.

partial excerpt

Materials and methods

We tested the effects of the most commonly used detergents on eight different TSE agents from different species and different forms of prion diseases.

The detergent influences the resistance of PrP to proteinase Kscience

PrPsciencePartial resistance to proteinase K is generally present in TSEs. Proteinase K serves to uncover previously hidden epitopes by loosening the structure of protein aggregates. As the pK concentration increases, the number of detectable aggregate residues decreases (McKinley et al., 1983). However, the PK resistance was also influenced by the detergent in the homogenate. While this is obvious when using SDS, it is less evident when using SLS and DOC without additional destabilizers


Our results underscore the fact that detergents commonly used in diagnostic assays may contribute to partial resistance of PrP to proteinase K.scienceDetergents have varying effects on PrP partially resistant to proteinase Kscience; may increase or decrease their detection. Factors affecting detection include the type of detergent, the concentration, the TSE-producing species and the form of the disease or the type of prion.

In TSEs that are resistant to denaturation, such as type 2 prions

(Video) Prion Diseases Simplified/SCRAPIE/CJD/BSE

Thank you

We would like to thank Manuela Becker for technical assistance and Niels Kruse and Joanna Gawinecka for assistance in densitometric analysis. The antibodies were provided courtesy of Dr. Michael Beekes of RKI Berlin and Dr. Dirk Motzkus of DPZ Göttingen. This work was supported byAlberta Prion Institutedo WJSS iStefanie Czub, head of the CFIA and OIE BSE National Reference Laboratory, Lethbridge, AlbertaAnd byNational Institute of Health PO1 AI 77774-01"Disease,


  • A.BusmanWait.

    Atypical scrapie cases in Germany and France identified by varying response patterns in a BSE rapid test

    J. Virus. method


  • Hong KongLasWait.

    The N-terminal cleavage site of PrPSc from BSE differs from the cleavage site of PrPSc from scrapie

    Biochemical. biophysics. tank. community.


  • congressmanMcKinleyaWait.

    Protease resistance protein is a structural component of scrapie prions



  • S.notaryWait.

    Effect of different experimental conditions on protease digestion of PrPSc cores: implications for typing and molecular classification of CJD strains

    J. Biology. Chemical.


  • SBPrussianWait.

    The scrapie prions fuse to form birefringent amyloid rods



  • WMWHOWait.

    Similarities between scrapie and Creutzfeldt-Jakob disease are encoded by different types of prions

    Nope. J. Pasol.


  • E.S.Williams

    scrapie and chronic wasting disease

    clinical. lab. medicine.


  • K. F.WinkhoferWait.

    Sensitive filter retention test for PrP(Sc) detection and screening of anti-prion compounds

    FEBS Express.


  • Z.ThanksWait.

    Chronic wasting disease and Creutzfeldt-Jakob disease in elk and deer: a comparative analysis of scrapie prions

    J. Biology. Chemical.


  • T.appealWait.

    Thermostability of prion rods and recombinant prion proteins in water, lipids and lipid-water mixtures

    J. General virus.


  • M.bixWait.

    Sequential appearance and accumulation of central nervous system markers in orally infected hamsters with ovine scrapie

    J. General virus.


  • S.L.Well doneWait.

    A Norwegian case of an unusually distinctive scrapie and the naming of a new type of Nor98

    veterinary. record.


  • special zoneBoltonWait.

    Identification of proteins purified from scrapie prions



  • SJEverestWait.

    Unusual prion proteins in sheep brains collected during UK scrapie surveillance programme

    J. General virus.


    (Video) Prion Diseases Analyzed by Transgenic Mouse Modeling by Glenn Telling

  • B.Horn LimanWait.

    Chemical disinfection and prion inactivation

  • M.KlingebornWait.

    Characterization of N- and C-terminally truncated proteinase K-resistant PrP in Nor98 atypical scrapie

    J. General virus.


  • Quoted by (15)

    • Nanodiscs formed from styrene-maleic acid copolymer derivatives help restore infectious prion multimers bound to brain-derived lipids

      2020, Journal of Biological Chemistry

      Excerpt from the quote:

      Prions are often membrane-bound by GPI anchors, although their endogenous lipid recruitment is not well understood. Prion analysis is based on maintaining high concentrations of conventional detergents such as sarcosyl (4, 5) despite inducing changes in structural properties (6), impaired interactions with physiological partners including heparin (7) and prion fibrosis including proteinase K (PK)– and mouse brain homogenates treated with phosphotungstic acid (PTA) and infected with Rocky Mountain Laboratories (RML) strains (8). The prevalence of these tests is due to the lack of a milder alternative that more gently releases intact prions: lipid assay kits (9).

      Prions are lipidated proteins that interact with endogenous lipids and metal ions. They also fuse into multimers and multiply into an infectious form of scrapie called PrPscience.High resolution structure of infectious PrPscienceThe status remains unknown, and its analysis was based mainly on detergent-based formulations free of endogenous ligands. In this case, our engineered polymer enables the isolation of the endogenous membrane: protein assemblies in native nanodiscs without exposure to traditional detergents that destabilize protein structures and induce fibrosis. The group of styrene-maleic acid (SMA) polymers, including methylamine derivatives, promotes mild release of infectious complexes to solve the problem of multimerization, while polymers containing a thiol group promote crystallization. Polymers extracted from brain homogenates of superprion-infected Syrian hamsters and Rocky Mountain Laboratory prion-infected WT mice produced infectious prion nanoparticles, including oligomers associated with lipid vesicles and microfilaments. Lipid analysis revealed cephalins associated with prion protofilaments and those phospholipids that were particularly enriched in prion assemblies captured by the methylamine-modified copolymer. PrP infectivity comparisonscienceAdhesion to SMA lipid molecules in mice and hamsters has shown that these amphiphilic polymers provide a valuable tool for the high-yield production of intact, detergent-free prions that retainLiveActivity. This natural method of prion isolation provides a way to produce related prions: target lipids and other proteins that can form multimeric assemblies and fibrils on membranes.

    • Prion decontamination

      2019, Decontamination in hospitals and healthcare

      Prions are infectious infectious agents, but are believed to be composed entirely of proteins. They present unique decontamination challenges as they can adsorb to surfaces and exhibit exceptional resistance to removal/inactivation. This review considers what is known about these drugs, their associated diseases, and their decontamination from reusable devices. The standard precautions inherent in infection prevention practice may reduce the risk of prion contamination, but may require healthcare professionals to change their mindset and expectations. In addition, several other neurodegenerative diseases have been shown to have similar "prion-like" mechanisms induced by iatrogens and highlight the importance of decontaminating misfolded proteins.

    • Parkinson Mobbs disease - a synaptic disorder?

      2014, Basal ganglia

      Excerpt from the quote:

      Paraffin-embedded tissue is sectioned in the same manner as conventional histology, but the slides are placed on nitrocellulose membranes. As a result of protease digestion with detergents, protein aggregates are mobilized from the tissue, bound to nitrocellulose membranes, and epitopes in aggregates are removed [43]. Protease-resistant aggregates are detected by antibodies and visualized in formazan reactions [42].

      Currently, the pathophysiology of Parkinson's disease is mainly explained by the loss of dopaminergic nerve cells leading to a deficiency of neurotransmitters. In the final phase, the substantia nigra shows a marked loss of neurons in Parkinson's disease. Lewy bodies can be found in some of the remaining neurons and serve as the pathological hallmark of the disease. These Lewy bodies are mainly composed of aggregated α-synuclein, a protein found physiologically in the presynapse. Lewy bodies are considered a pathophysiologically significant form of α-synuclein pathology because their presence coincides with the loss of neurons in the substantia nigra.

      As clinical signs suggest synaptic pathology, presynaptic involvement in the pathology of alpha-synuclein aggregation has recently been identified. One to two orders of magnitude more α-synuclein aggregates than Lewy bodies or Lewy neurites can be found presynaptically. Dendritic spine degeneration associated with α-synuclein synaptic polymerization pathology has been shown to occur in human diseases. In experiments using transgenic mice or cell cultures, mild (2- to 3-fold) overexpression of α-synuclein resulted in altered vesicle turnover and reduced neurotransmitter release. Various approaches have linked these changes to presynaptic α-synuclein aggregation.

      These findings could fundamentally change the concept of the pathophysiology of Parkinson's disease. It is not the loss of nerve cells, but the synaptic dysfunction of the remaining nerve cells that should be the focus. Future therapeutic strategies should focus on synapse maintenance rather than cell death mechanisms or cell replacement strategies.

    • Prion decontamination

      2013, Decontamination in hospitals and healthcare

      (Video) Virology Lectures 2020 #25: Unusual infectious agents

      Prions are infectious infectious agents, but are believed to be composed entirely of proteins. They present a unique decontamination challenge as they can absorb onto surfaces and show considerable resistance to removal/inactivation. This review considers what is known about these drugs, their associated diseases, and their decontamination from reusable devices. The standard precautions inherent in infection prevention practice may reduce the risk of prion contamination, but may require healthcare professionals to change their mindset and expectations.

    • Polythiophenes inhibit prion propagation by stabilizing prion protein (PrP) aggregates.

      2012, Journal of Biological Chemistry

      Excerpt from the quote:

      PTAA also caused a leftward shift in the conformational stability curve of PrPSc upon exposure to increasing concentrations of the non-surfactant chaotrope GdnHCl. This concentration-dependent behavior of LCP is similar to the mechanism described for several surfactants that are thought to affect protein aggregation in the two-concentration regime by interacting as single molecules or in equilibrium with small molecule aggregates (52) and have been shown to enhance or decrease the stability and detection of PK-resistant PrPSc (18, 53, 54). Concentration-dependent interactions of surfactants with aggregated proteins can result in conformational diversity.

      Luminescent conjugated polymers (LCPs) interact with ordered protein aggregates and sensitively detect amyloid from a wide variety of proteins, suggesting that they may have antiprion properties. Here we show that various anionic, cationic and zwitterionic LCPs reduce the infectivity of prion-containing brain homogenates and prion-infected sections of cerebellar organotypic cultures and reduce the number of prion scrapie subtypes PrPC(PrPscience) oligomers that can be captured in affinity assays. Paradoxically, the treatment increased resistance to PrPscienceProteolysis triggers densification and increases the proteolytic resistance of recombinant murine PrP fibers (23–231). These results suggest that LCP acts as an antiprion agent, converting PrP aggregates into a less brittle structure. In addition, ELISA on culture sections of cerebellar organs andin vitroPrP conversion assays (23–231) in mice suggest that poly(thiophene-3-acetic acid) may also interfere with PrP productionscienceBy stabilizing the PrP conformationCor intermediates. Thus, LCPs represent a new class of antiprion agents whose mode of action appears to depend on hyperstabilization rather than destabilization of PrP.sciencedeposit.

    View all citing articles on Scopus

    Featured Articles (6)

    • science article

      Basement membrane protein nidogen-1 is a target of meprin-β in cisplatin nephrotoxicity

      Toxicology Letters, Volume 236, Issue 2, 2015, pages 110-116

      Meprin is an oligomeric metalloprotease that is abundantly expressed in the brush border membrane of the proximal renal tubules. During acute kidney injury induced by cisplatin or ischemia-reperfusion (AKI), membrane-bound meprin is shed and its location changes from the apical membrane to the basolateral surface of the proximal tubules. meprin cleaves basement membrane proteinsin vitroHowever, it is not clear whether hypnotics are able to degrade extracellular matrix proteins under pathophysiological conditionsLiveThe present study shows that the basement membrane protein nidogen-1 is cleaved and excreted in the urine of mice subjected to cisplatin-induced nephrotoxicity (AKI model). Cleaved nidogen-1 was not detected in the urine of untreated mice, but the excretion of cleaved nidogen-1 increased in a time-dependent manner during the progression of cisplatin nephrotoxicity. Urinary excretion of cleaved nidogen-1 was significantly blocked by the meprin inhibitor actinin. Moreover, excretion of cleaved nidogen-1 was significantly inhibited in meprin-β-deficient mice, but not in meprin-α-deficient mice subjected to cisplatin nephrotoxicity, further suggesting that merin-β is involved in nidogen-1 cleavage. These studies provide strong evidence of a pathophysiological link between meprin-β and urinary excretion of cleaved nidogen-1 during cisplatin-induced AKI.

    • science article

      Localization of neurotrophins and their receptors in the adult mouse brain and their role in the pathogenesis of a transgenic mouse model of bovine spongiform encephalopathy

      Journal of Comparative Pathology, tom 150, numer 4, 2014, strony 449-462

      Neurotrophic factors are a family of growth factors that act on nerve cells. Neurotrophic factors include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophic factors (NT)-3, -4 and -5. The action of neurotrophins depends on two transmembrane receptor signaling systems: (1) the tropomyosin-related tyrosine kinase (Trk) family of receptors (Trk A, Trk B and Trk C) and (2) the p75 neurotrophin receptor (p75NTRInteractions between neurotrophic factors and their receptors may be involved in the mechanisms mediating differential susceptibility of neuronal populations to neurodegenerative diseases. The aim of this study was to evaluate the role of neurotrophins in the pathogenesis of bovine spongiform encephalopathy (BSE), using transgenic mice overexpressing bovineprnp(BoTg 110). Histochemiaedible tomatoLectin, hematoxylin and eosin staining and immunohistochemistry for abnormal prion protein (PrP) isoformsD), glial fibrillary acidic protein (GFAP), NGF, BDNF, NT-3 and receptors Trk A, Trk B, Trk C and p75NTRConducted. Lesions and immunolabelling patterns were assessed semi-quantitatively in different brain regions. With the exception of p75, there were no significant differences in the immunolabeling of neurotrophins and their receptors between BSE vaccinated animals and control animalsNTR, indicating an increased expression associated with damage distribution, PrPDDeposition and gliosis in BSE vaccinated mice.

      (Video) Virology Lectures 2023 #24: Unusual infectious agents
    • science article

      Cost savings during optimized infliximab remission in patients with Crohn's disease using a test-based de-escalation strategy: a discrete event modeling study

      Gastrointestinal and Liver Diseases, Volume 51, Issue 1, 2019, Pages 112-119

      De-escalation should be considered in patients with Crohn's disease who have achieved sustained remission after optimized infliximab therapy.

      We developed a model to assess the magnitude of cost savings over the course of a patient's illness, guided by infliximab trough levels with and without drug de-escalation.

      We designed 4 virtual cohorts (P1 – P4) in which 10,000 patients were in clinical remission after optimized infliximab therapy and followed for 2 years. P1: No drug reduction - 10 mg/kg/8 weeks; P2: Reduction of drug dose from 10 mg/kg/8 weeks to 5 mg/kg/8 weeks depending on valley level; P3: No drug reduction - 10 mg/kg/8 weeks 6 weeks; P4: Depending on the trough level, the drug dose is reduced from 10 mg/kg/6 weeks to 10 mg/kg/8 weeks. For cohorts P2 and P4, a decision was made to lower if the trough level was ≥7 μg/ml and not to reduce if the trough level was <7 μg/ml. Only drug administration costs are included.

      The cost differences when comparing P1 to P2 and P3 to P4 were 7.6% and 4.6% respectively, representing cost savings of €30.5 million and €20.3 million for 10,000 patients.

      Over a 2-year period, downgrading infliximab to trough levels resulted in cost savings of around 6%, equivalent to around €25.4 million.

    • science article

      Estimating the food chain impact of removing bovine tonsils from specified risk material in the UK, assuming a negligible risk status for bovine spongiform encephalopathy

      Food Control, Volume 94, 2018, pages 341-344

      The earliest estimate of the UK (GB) as a whole achieving Negative Risk (NR) status for bovine spongiform encephalopathy (BSE) is 2021. This status allows certain tissues, such as bovine tonsils, to cease being designated as Specified Risk Material (SRM) . The BSE control model was used to estimate the effect of any additional lingual tonsil material from harvested tongues that inadvertently entered the human food chain on the amount of infectivity consumed. Using the baseline model, tonsils were classified as SRM with a mean of 0.08 for bovine oral (BO) ID50GB is estimated to enter the food chain in just over a year. It is estimated that in the state of NR this average will increase to 0.83 BO ID50although this corresponds to a 10-fold increase in BO ID50Since the probability of infected animals being present in a healthy slaughter population in 2017 is very low, this number remains low. The model makes a number of assumptions about the number of lingual tonsils that inadvertently enter the food chain and the infectious titer in this particular tonsil material.

    • science article

      Influence of breed and genotype on the occurrence and distribution of infectious and pathogenic prions after oral infection of sheep with the bovine spongiform encephalopathy pathogen

      Journal of Comparative Pathology, t. 152, nr 1, 2015, strony 28-40

      Infectious and disease-specific prion protein (PrPD) accumulation of the ARQ/ARQ, ARQ/ARR and ARR/ARR prion protein genes was studied in Romney and Suffolk sheep (Stomach) genotype (where A is alanine, R is arginine and Q is glutamine in PrP codons 136, 154 and 171), in experimental studies with bovine spongiform encephalopathy (BSE) agents of bovine origin after oral infection. Groups of sheep are routinely killed and mass tissues taken for mouse bioassays or immunohistochemistry (IHC) or both. Infectivity bioassay results were generally consistent with PrP resultsDTissue IHC and time after infection. nor PrPDNo infectivity was detected in any tissue from ARQ/ARR or ARR/ARR BSE-treated sheep or untreated controls. In addition, four ARQ/ARQ Suffolk ewes were heterozygous for methionine (M)/threonine at codon 112.Stomachgene showed no biological or immunohistochemical evidence of infection, while methionine homozygotes (MARQ/MARQ) did. In both MARQ/MARQ sheep breeds, the initial PrPDAccumulation occurs in the tissues of the lymphoreticular system (LRS), then in the central nervous system (CNS) and enteric nervous system (ENS), and finally in the autonomic and peripheral nervous systems and other organs. Infectivity detection closely mimics this sequence. no PrPDThis was observed in the ENS prior to its accumulation in the CNS, suggesting that ENS involvement occurs simultaneously with CNS involvement or subsequent centrifugal diffusion from the CNS. PrP distributionDWithin the ENS, further evidence has emerged of progressive spread from the ileal plexus to other segments of the ENS via neural connections across the intestinal wall. The two breeds differed in the involvement of LRS and ENS tissues, with Romney ewes showing more delayed and inconsistent PrPDAccumulation in this organization is greater than that of the Suffolk sheep. Whether this explains the slight delay (~5 months) in the onset of clinical signs in the Romney ewes is debatable as both breeds showed extensive accumulation and similar PrP at the last scheduled slaughter before the animals reached the size of the clinical endpointDaccumulate in the brain.

    • science article

      Vitamin D: its impact on disease and the microbiome

      The evolving microbiome, 2020, pp. 183-194

      Vitamin D deficiency is one of the most common micronutrient deficiencies affecting infants and children. Premature infants are particularly vulnerable to deficiencies that affect not only bone health, but also sepsis, atopy, and necrotizing enterocolitis. Vitamin D is increasingly recognized as an important regulator of the innate immune system and the gut microbiome. The therapeutic implications of vitamin D for the gut microbiome, infant health, and immune disorders such as inflammatory bowel disease are increasingly being researched.

      (Video) 2019 Keynote Speaker Richard Knight - Prion Diseases, An Overview
    see full text

    Copyright © 2011 Elsevier B.V. Published by Elsevier B.V. All rights reserved.


    What protein PrP implicated in transmissible spongiform encephalopathies? ›

    Transmissible spongiform encephalopathies (TSEs), or prion diseases, are invariably fatal neurodegenerative diseases of humans and animals. TSEs are believed to be caused by neuronal accumulation of a protease-resistant abnormal conformer of a host-encoded protein known as prion protein.

    What disease agents are infectious proteins that can cause transmissible spongiform encephalopathies? ›

    The causative agents of TSEs are believed to be prions. The term “prions” refers to abnormal, pathogenic agents that are transmissible and are able to induce abnormal folding of specific normal cellular proteins called prion proteins that are found most abundantly in the brain.

    What causes PrPSc? ›

    The abnormal PrPSc protein can be caused by a genetic mutation, or it can be acquired by eating food that contains the PrPSc protein, such as beef contaminated with the nervous tissue of cattle that had bovine spongiform encephalopathy.

    Is PrPSc protease-resistant? ›

    Brain-derived and recombinant PrPSc are known to withstand high concentrations of protease treatment (14, 16). The protease-resistant subpopulation of PrPSc (PrPres) encompasses a C-terminal PrP fragment starting at around residue 90, with the exact position depending upon the prion strain.

    What proteins are PrPSc sensitive to? ›

    Sodium hydroxide renders the prion protein PrPSc sensitive to proteinase K.

    What are the symptoms of PRNP? ›

    The major features of these diseases include changes in memory, personality, and behavior; a decline in intellectual function (dementia); and abnormal movements, particularly difficulty with coordinating movements (ataxia). The signs and symptoms worsen over time, ultimately leading to death.

    Can you get prion disease from eating brain? ›

    Kuru. This disease is seen in New Guinea. It's caused by eating human brain tissue contaminated with infectious prions. Because of increased awareness about the disease and how it is transmitted, kuru is now rare.

    What are the examples of TSE disease? ›

    TSEs include:
    • Classical and atypical bovine spongiform encephalopathy (BSE) in cattle;
    • Classical and atypical scrapie in sheep and goats;
    • Chronic wasting disease (CWD) in cervids;
    • Transmissible mink encephalopathy (TME) in mink;
    • Feline spongiform encephalopathy (FSE) in cats;
    Apr 17, 2023

    What is the cause of TSE disease? ›

    TSEs are believed to be caused by prions, abnormally folded proteins, that build up in the brain causing brain damage and the characteristic symptoms associated with the disease.

    What diseases are associated with PrPSc accumulation? ›

    Prion diseases are a group of fatal neurodegenerative disorders that are caused by the transmissible misfolded isoform (PrPSc) of the cellular prion (PrPC) [1], including Creutzfeldt-Jakob disease of humans, bovine spongiform encephalopathy, and scrapie of sheep.

    How do you get rid of prions? ›

    To destroy a prion it must be denatured to the point that it can no longer cause normal proteins to misfold. Sustained heat for several hours at extremely high temperatures (900°F and above) will reliably destroy a prion.

    Where does PrPSc accumulate? ›

    In prion diseases, host prion protein is misfolded to form a pathogenic protease-resistant form, PrPSc, which accumulates in neurons, astroglia and microglia in the CNS.

    How does PrPSc spread? ›

    Prions Can Be Shed into the Environment and Can Remain Infectious. On the farm and amongst free-ranging animals the horizontal transmission prions most likely occurs via the ingestion of contaminated pasture.

    How do you protect proteins from protease? ›

    Keep everything cold

    Cell lysis and extraction are best carried out at low temperatures. Typically, an extraction buffer is ice cold and lysed cells are kept on ice until centrifugation. The low temperature slows the action of proteases.

    What diseases are protease in? ›

    Proteases are highly regulated (e.g. transcriptionally, post-translationally, activated, inhibited, and compartmentalized). Proteases are involved in many diseases (e.g. cancer, Alzheimer's, arthritis, blood clotting disorders, allergies, and infections, to name a few).

    What is the difference between PrP and PrPSc? ›

    PrPSc has the same primary structure as PrPC but a different fold (16). During the conversion of PrPC to PrPSc, the a-helix content decreases somewhat but the b-sheet content increases greatly (17,18). Also, whereas PrPC is protease sensitive, PrPSc contains a protease-resistant core of residues ~90–230 (19).

    What does PrPSc protein do? ›

    There are now a number of studies suggesting that PrPC can activate transmembrane signaling pathways involved in several different phenomena, including neuronal survival, neurite outgrowth, and neurotoxicity.

    What is the prion disease PrPSc? ›

    PrPSc (scrapie isoform of the prion protein) prions are the infectious agent behind diseases such as Creutzfeldt–Jakob disease in humans, bovine spongiform encephalopathy in cattle, chronic wasting disease in cervids (deer, elk, moose, and reindeer), as well as goat and sheep scrapie.

    What does prion disease feel like? ›

    Typical symptoms include imbalance and incoordination, memory loss and impaired thinking, and psychiatric symptoms such as anxiety or depression. Once the symptoms do appear, CJD progresses very quickly and is usually fatal within a few months of symptom onset.

    What are 5 diseases caused by prions? ›

    Animal prion diseases include:
    • Bovine spongiform encephalopathy, also called mad cow disease; this is the only type that can spread to humans.
    • Chronic wasting disease.
    • Scrapie.
    • Transmissible mink encephalopathy.
    • Feline spongiform encephalopathy.
    • Ungulate spongiform encephalopathy (found in deer and related animals)

    How long can you live with prion disease? ›

    Although the survival time is variable in prion diseases, the average duration is 4-6 months. Hence, a diagnosis of prion disease alone should be sufficient for hospice enrollment.

    Is dementia a prion disease? ›

    Prion diseases cause dementia, but not Alzheimer's disease. Different genes and proteins are involved in Alzheimer's. But in all these diseases, including Alzheimer's, the cause is proteins that don't work the way they should and damage brain cells.

    Why are prions so scary? ›

    “Prions are distorted versions of normal proteins found in human and animal brain and other tissues,” explains Colorado State University's Prion Research Center. “These distorted ('misfolded') proteins damage brain cells, leading to fatal dementias akin to human Alzheimer's and Parkinson's diseases.”

    Does prion disease lead to dementia? ›

    Creutzfeldt-Jakob disease causes a type of dementia that gets worse unusually fast. More common causes of dementia, such as Alzheimer's, dementia with Lewy bodies and frontotemporal dementia, typically progress more slowly. Through a process scientists don't yet understand, misfolded prion protein destroys brain cells.

    Is Alzheimer's a prion disease? ›

    Prion diseases are caused by the toxic misfolding and clumping of the prion protein, PrP. Although Alzheimer's is not a prion disease, and the PrP, Aβ, and tau proteins each normally fold into distinct 3D shapes, upon misfolding, all three proteins can all form aggregates that have a very specific structural pattern.

    What is one example of a disease caused by a prion? ›

    This process – which can be underway for years before symptoms appear – likely causes the most common form of prion disease in people, sporadic Creutzfeldt-Jakob disease (CJD). Other forms of human prion diseases include variant CJD, fatal familial insomnia, Gerstmann-Straussler-Scheinker Syndrome and Kuru.

    What is the most common transmissible spongiform encephalopathy? ›

    Creutzfeldt-Jakob disease (CJD) is the most well-known of the human TSEs.

    How do prion diseases affect the central nervous system? ›

    PrPC is present in all cells of the body but has a high concentration in the brain. Consequently, most prion diseases affect the nervous system predominantly or exclusively. The most common change caused by prions is the formation of tiny bubbles in brain cells, and the brain becomes filled with microscopic holes.

    How do you treat transmissible spongiform encephalopathy? ›

    Currently, there is no treatment for TSEs. If you suspect that an animal is infected: they should be quarantined, culled and tested.

    What part of the nervous system is most affected by fatal familial insomnia? ›

    FFI is described to mainly affect the thalamus with a propensity for anterior ventral and mediodorsal thalamic nuclei. Other parts of the brain, including the inferior olives of the medulla oblongata and the cerebral cortex, have also been shown to be involved.

    How is PrPSc protein able to act as infectious agent? ›

    The conversion of PrPC to PrPSc. The protein only hypothesis of prion conversion posits that misfolded PrPSc acts a catalyst, directly binding to PrPC and causing its conversion to PrPSc. This self-perpetuating recruitment leads to large aggregates of PrPSc, and underlies its infectious potential.

    How can abnormal forms of the prion protein arise within an individual? ›

    In the hereditary form, infectious prions can arise when a mutation occurs in the gene for the body's normal prion protein. As the mutated PrPC duplicates itself, it spontaneously changes shape into the infectious form.

    Can prions be washed off skin? ›

    Prions are very stable molecules that do not break down easily. Normal sterilization procedures such as cooking, washing and boiling do not destroy them.

    What is the new treatment for prion disease? ›

    Researchers at the MRC Prion Unit at UCL have developed a monoclonal antibody, called PRN100, which was given to six UCLH patients with CJD between October 2018 and July 2019. The results, published in the Lancet Neurology, show the treatment is safe and able to access the brain.

    Has anyone ever survived a prion disease? ›

    Simms died at the age of 27. He is the world's longest known survivor of Creutrzfeldt-Jakob disease. How it worked: Prion proteins exist in at least two forms: PrPC (PrP = prion, C = cellular), a harmless form, and PrPSC (PrP = prion, SC = scrapie), which causes disease.

    How do prions get into the brain? ›

    Prions reach the central nervous system (CNS) through autonomic nerves, directly after intracerebral inoculation, or via aerosols through immune-independent pathways.

    Is A prion A virus? ›

    Finally, we discuss prions. These infectious agents were originally believed to be anomalous viruses, hence their inclusion here. However, they consist solely of protein, with no enclosed nucleic acid. Thus, they are definitely not viruses despite sharing the superficial properties of size and infectiousness.

    Can prions spread through touch? ›

    Although ingestion of surface-bound prions is the most likely route of environmental prion transmission, our data indicate that transmission can also occur by physical contact through rubbing or licking.

    What are the proteins implicated in spongiform encephalopathy? ›

    Bovine Spongiform Encephalopathy (BSE), or Mad Cow Disease

    Currently, the most accepted theory is that the agent is a modified form of a normal protein known as prion protein.

    What is the protein structure of PrP prion? ›

    PrPC attaches to the outer surface of the cell membrane by a glycosylphosphatidylinositol anchor at its C-terminal Ser231. Prion protein contains five octapeptide repeats with sequence PHGGGWGQ (though the first repeat has the slightly-modified, histidine-deficient sequence PQGGGGWGQ).

    What protein is involved in prion disease? ›

    What causes prion disease? Prion diseases occur when normal prion protein, found on the surface of many cells, becomes abnormal and clump in the brain, causing brain damage. This abnormal accumulation of protein in the brain can cause memory impairment, personality changes, and difficulties with movement.

    What is PrP in prion disease? ›

    Prion diseases are a group of fatal neurodegenerative disorders caused by the misfolding of the cellular prion protein (PrPC) into a pathogenic conformation (PrPSc). PrPSc is capable of folding into multiple self-replicating prion strains that produce phenotypically distinct neurological disorders.


    1. Virology Lectures 2021 #24 - Unusual Infectious Agents
    (Vincent Racaniello)
    2. The zoonotic potential of chronic wasting disease | OCS Science Seminar
    (Alberta Environment and Protected Areas)
    3. Grand Rounds. A clinical update on Prion Disease. Dr. Suvankar Pal. 4/22/2022
    (Downstate Neurology)
    4. Confronting CJD & other Prion Disoders
    (Creutzfeldt Jakob)
    5. Darwinian Evolution of Prions
    (Scripps Research)
    6. 141 - Neurology - Dr. Raymond Roos | Virtual Pre-Health Shadowing
    (Pre-Health Shadowing)


    Top Articles
    Latest Posts
    Article information

    Author: Nathanial Hackett

    Last Updated: 11/26/2023

    Views: 5825

    Rating: 4.1 / 5 (72 voted)

    Reviews: 87% of readers found this page helpful

    Author information

    Name: Nathanial Hackett

    Birthday: 1997-10-09

    Address: Apt. 935 264 Abshire Canyon, South Nerissachester, NM 01800

    Phone: +9752624861224

    Job: Forward Technology Assistant

    Hobby: Listening to music, Shopping, Vacation, Baton twirling, Flower arranging, Blacksmithing, Do it yourself

    Introduction: My name is Nathanial Hackett, I am a lovely, curious, smiling, lively, thoughtful, courageous, lively person who loves writing and wants to share my knowledge and understanding with you.