Journal articles: 'Prion conversion'

1

Jones, Rachel. "Blocking prion conversion." Nature Reviews Neuroscience 2, no. 9 (September 2001): 605. http://dx.doi.org/10.1038/35090100.

Full text

APA, Harvard, Vancouver, ISO, and other styles

2

Zhou, Z., and G. Xiao. "Conformational conversion of prion protein in prion diseases." Acta Biochimica et Biophysica Sinica 45, no. 6 (April 11, 2013): 465–76. http://dx.doi.org/10.1093/abbs/gmt027.

Full text

APA, Harvard, Vancouver, ISO, and other styles

3

Hara, Hideyuki, and Suehiro Sakaguchi. "Virus Infection, Genetic Mutations, and Prion Infection in Prion Protein Conversion." International Journal of Molecular Sciences 22, no. 22 (November 18, 2021): 12439. http://dx.doi.org/10.3390/ijms222212439.

Full text

Abstract:

Conformational conversion of the cellular isoform of prion protein, PrPC, into the abnormally folded, amyloidogenic isoform, PrPSc, is an underlying pathogenic mechanism in prion diseases. The diseases manifest as sporadic, hereditary, and acquired disorders. Etiological mechanisms driving the conversion of PrPC into PrPSc are unknown in sporadic prion diseases, while prion infection and specific mutations in the PrP gene are known to cause the conversion of PrPC into PrPSc in acquired and hereditary prion diseases, respectively. We recently reported that a neurotropic strain of influenza A virus (IAV) induced the conversion of PrPC into PrPSc as well as formation of infectious prions in mouse neuroblastoma cells after infection, suggesting the causative role of the neuronal infection of IAV in sporadic prion diseases. Here, we discuss the conversion mechanism of PrPC into PrPSc in different types of prion diseases, by presenting our findings of the IAV infection-induced conversion of PrPC into PrPSc and by reviewing the so far reported transgenic animal models of hereditary prion diseases and the reverse genetic studies, which have revealed the structure-function relationship for PrPC to convert into PrPSc after prion infection.

APA, Harvard, Vancouver, ISO, and other styles

4

Rigter, Alan, Jan Priem, Drophatie Timmers-Parohi, Jan PM Langeveld, Fred G. van Zijderveld, and Alex Bossers. "Prion protein self-peptides modulate prion interactions and conversion." BMC Biochemistry 10, no. 1 (2009): 29. http://dx.doi.org/10.1186/1471-2091-10-29.

Full text

APA, Harvard, Vancouver, ISO, and other styles

5

Shen, Liang, and Hong-Fang Ji. "Conformational conversion and prion disease." Nature Reviews Molecular Cell Biology 12, no. 4 (March 23, 2011): 273. http://dx.doi.org/10.1038/nrm3007-c1.

Full text

APA, Harvard, Vancouver, ISO, and other styles

6

Supattapone, Surachai. "Prion protein conversion in vitro." Journal of Molecular Medicine 82, no. 6 (June 1, 2004): 348–56. http://dx.doi.org/10.1007/s00109-004-0534-3.

Full text

APA, Harvard, Vancouver, ISO, and other styles

7

Deleault, Nathan R., Ralf W. Lucassen, and Surachai Supattapone. "RNA molecules stimulate prion protein conversion." Nature 425, no. 6959 (October 2003): 717–20. http://dx.doi.org/10.1038/nature01979.

Full text

APA, Harvard, Vancouver, ISO, and other styles

8

Apostol, Marcin I., and Witold K. Surewicz. "Structural Underpinnings of Prion Protein Conversion." Journal of Biological Chemistry 286, no. 21 (May 20, 2011): le7. http://dx.doi.org/10.1074/jbc.l110.213926.

Full text

APA, Harvard, Vancouver, ISO, and other styles

9

Kang, Hae-Eun, Youngwon Mo, Raihah Abd Rahim, Hye-Mi Lee, and Chongsuk Ryou. "Prion Diagnosis: Application of Real-Time Quaking-Induced Conversion." BioMed Research International 2017 (2017): 1–8. http://dx.doi.org/10.1155/2017/5413936.

Full text

Abstract:

Prions composed of pathogenic scrapie prion protein (PrPSc) are infectious pathogens that cause progressive neurological conditions known as prion diseases or transmissible spongiform encephalopathies. Although these diseases pose considerable risk to public health, procedures for early diagnosis have not been established. One of the most recent attempts at sensitive and specific detection of prions is the real-time quaking-induced conversion (RT-QuIC) method, which measures the activity of PrPScaggregates or amyloid formation triggered by PrPScseeds in the presence of recombinant PrP. In this review, we summarize prions, prion diseases, and current approaches to diagnosis, including the principle, conditions for assay performance, and current diagnostic applications of RT-QuIC.

APA, Harvard, Vancouver, ISO, and other styles

10

Engelke, Anna D., Anika Gonsberg, Simrika Thapa, Sebastian Jung, Sarah Ulbrich, Ralf Seidel, Shaon Basu, et al. "Dimerization of the cellular prion protein inhibits propagation of scrapie prions." Journal of Biological Chemistry 293, no. 21 (April 10, 2018): 8020–31. http://dx.doi.org/10.1074/jbc.ra117.000990.

Full text

Abstract:

A central step in the pathogenesis of prion diseases is the conformational transition of the cellular prion protein (PrPC) into the scrapie isoform, denoted PrPSc. Studies in transgenic mice have indicated that this conversion requires a direct interaction between PrPC and PrPSc; however, insights into the underlying mechanisms are still missing. Interestingly, only a subfraction of PrPC is converted in scrapie-infected cells, suggesting that not all PrPC species are suitable substrates for the conversion. On the basis of the observation that PrPC can form homodimers under physiological conditions with the internal hydrophobic domain (HD) serving as a putative dimerization domain, we wondered whether PrP dimerization is involved in the formation of neurotoxic and/or infectious PrP conformers. Here, we analyzed the possible impact on dimerization of pathogenic mutations in the HD that induce a spontaneous neurodegenerative disease in transgenic mice. Similarly to wildtype (WT) PrPC, the neurotoxic variant PrP(AV3) formed homodimers as well as heterodimers with WTPrPC. Notably, forced PrP dimerization via an intermolecular disulfide bond did not interfere with its maturation and intracellular trafficking. Covalently linked PrP dimers were complex glycosylated, GPI-anchored, and sorted to the outer leaflet of the plasma membrane. However, forced PrPC dimerization completely blocked its conversion into PrPSc in chronically scrapie-infected mouse neuroblastoma cells. Moreover, PrPC dimers had a dominant-negative inhibition effect on the conversion of monomeric PrPC. Our findings suggest that PrPC monomers are the major substrates for PrPSc propagation and that it may be possible to halt prion formation by stabilizing PrPC dimers.

APA, Harvard, Vancouver, ISO, and other styles

11

Davenport, Kristen A., Davin M. Henderson, Candace K. Mathiason, and Edward A. Hoover. "Assessment of the PrP c Amino-Terminal Domain in Prion Species Barriers." Journal of Virology 90, no. 23 (September 21, 2016): 10752–61. http://dx.doi.org/10.1128/jvi.01121-16.

Full text

Abstract:

ABSTRACT Chronic wasting disease (CWD) in cervids and bovine spongiform encephalopathy (BSE) in cattle are prion diseases that are caused by the same protein-misfolding mechanism, but they appear to pose different risks to humans. We are interested in understanding the differences between the species barriers of CWD and BSE. We used real-time, quaking-induced conversion (RT-QuIC) to model the central molecular event in prion disease, the templated misfolding of the normal prion protein, PrP c , to a pathogenic, amyloid isoform, scrapie prion protein, PrP Sc . We examined the role of the PrP c amino-terminal domain (N-terminal domain [NTD], amino acids [aa] 23 to 90) in cross-species conversion by comparing the conversion efficiency of various prion seeds in either full-length (aa 23 to 231) or truncated (aa 90 to 231) PrP c . We demonstrate that the presence of white-tailed deer and bovine NTDs hindered seeded conversion of PrP c , but human and bank vole NTDs did the opposite. Additionally, full-length human and bank vole PrP c s were more likely to be converted to amyloid by CWD prions than were their truncated forms. A chimera with replacement of the human NTD by the bovine NTD resembled human PrP c . The requirement for an NTD, but not for the specific human sequence, suggests that the NTD interacts with other regions of the human PrP c to increase promiscuity. These data contribute to the evidence that, in addition to primary sequence, prion species barriers are controlled by interactions of the substrate NTD with the rest of the substrate PrP c molecule. IMPORTANCE We demonstrate that the amino-terminal domain of the normal prion protein, PrP c , hinders seeded conversion of bovine and white-tailed deer PrP c s to the prion forms, but it facilitates conversion of the human and bank vole PrP c s to the prion forms. Additionally, we demonstrate that the amino-terminal domain of human and bank vole PrP c s requires interaction with the rest of the molecule to facilitate conversion by CWD prions. These data suggest that interactions of the amino-terminal domain with the rest of the PrP c molecule play an important role in the susceptibility of humans to CWD prions.

APA, Harvard, Vancouver, ISO, and other styles

12

Tahir, Waqas, Basant Abdulrahman, Dalia H. Abdelaziz, Simrika Thapa, Rupali Walia, and Hermann M. Schätzl. "An astrocyte cell line that differentially propagates murine prions." Journal of Biological Chemistry 295, no. 33 (June 19, 2020): 11572–83. http://dx.doi.org/10.1074/jbc.ra120.012596.

Full text

Abstract:

Prion diseases are fatal infectious neurodegenerative disorders in human and animals caused by misfolding of the cellular prion protein (PrPC) into the pathological isoform PrPSc. Elucidating the molecular and cellular mechanisms underlying prion propagation may help to develop disease interventions. Cell culture systems for prion propagation have greatly advanced molecular insights into prion biology, but translation of in vitro to in vivo findings is often disappointing. A wider range of cell culture systems might help overcome these shortcomings. Here, we describe an immortalized mouse neuronal astrocyte cell line (C8D1A) that can be infected with murine prions. Both PrPC protein and mRNA levels in astrocytes were comparable with those in neuronal and non-neuronal cell lines permitting persistent prion infection. We challenged astrocytes with three mouse-adapted prion strains (22L, RML, and ME7) and cultured them for six passages. Immunoblotting results revealed that the astrocytes propagated 22L prions well over all six passages, whereas ME7 prions did not replicate, and RML prions replicated only very weakly after five passages. Immunofluorescence analysis indicated similar results for PrPSc. Interestingly, when we used prion conversion activity as a readout in real-time quaking-induced conversion assays with RML-infected cell lysates, we observed a strong signal over all six passages, comparable with that for 22L-infected cells. These data indicate that the C8D1A cell line is permissive to prion infection. Moreover, the propagated prions differed in conversion and proteinase K–resistance levels in these astrocytes. We propose that the C8D1A cell line could be used to decipher prion strain biology.

APA, Harvard, Vancouver, ISO, and other styles

13

Fernández, María Rosario, Cristina Batlle, Marcos Gil-García, and Salvador Ventura. "Amyloid cores in prion domains: Key regulators for prion conformational conversion." Prion 11, no. 1 (January 2, 2017): 31–39. http://dx.doi.org/10.1080/19336896.2017.1282020.

Full text

APA, Harvard, Vancouver, ISO, and other styles

14

Legname, Giuseppe. "Copper coordination modulates prion conversion and infectivity in mammalian prion proteins." Prion 17, no. 1 (January 3, 2023): 1–6. http://dx.doi.org/10.1080/19336896.2022.2163835.

Full text

APA, Harvard, Vancouver, ISO, and other styles

15

Uchiyama, Keiji, Hironori Miyata, Yoshitaka Yamaguchi, Morikazu Imamura, Mariya Okazaki, Agriani Dini Pasiana, Junji Chida, et al. "Strain-Dependent Prion Infection in Mice Expressing Prion Protein with Deletion of Central Residues 91–106." International Journal of Molecular Sciences 21, no. 19 (October 1, 2020): 7260. http://dx.doi.org/10.3390/ijms21197260.

Full text

Abstract:

Conformational conversion of the cellular prion protein, PrPC, into the abnormally folded isoform, PrPSc, is a key pathogenic event in prion diseases. However, the exact conversion mechanism remains largely unknown. Transgenic mice expressing PrP with a deletion of the central residues 91–106 were generated in the absence of endogenous PrPC, designated Tg(PrP∆91–106)/Prnp0/0 mice and intracerebrally inoculated with various prions. Tg(PrP∆91–106)/Prnp0/0 mice were resistant to RML, 22L and FK-1 prions, neither producing PrPSc∆91–106 or prions in the brain nor developing disease after inoculation. However, they remained marginally susceptible to bovine spongiform encephalopathy (BSE) prions, developing disease after elongated incubation times and accumulating PrPSc∆91–106 and prions in the brain after inoculation with BSE prions. Recombinant PrP∆91-104 converted into PrPSc∆91–104 after incubation with BSE-PrPSc-prions but not with RML- and 22L–PrPSc-prions, in a protein misfolding cyclic amplification assay. However, digitonin and heparin stimulated the conversion of PrP∆91–104 into PrPSc∆91–104 even after incubation with RML- and 22L-PrPSc-prions. These results suggest that residues 91–106 or 91–104 of PrPC are crucially involved in prion pathogenesis in a strain-dependent manner and may play a similar role to digitonin and heparin in the conversion of PrPC into PrPSc.

APA, Harvard, Vancouver, ISO, and other styles

16

Davenport, Kristen A., Davin M. Henderson, Jifeng Bian, Glenn C. Telling, Candace K. Mathiason, and Edward A. Hoover. "Insights into Chronic Wasting Disease and Bovine Spongiform Encephalopathy Species Barriers by Use of Real-Time Conversion." Journal of Virology 89, no. 18 (July 8, 2015): 9524–31. http://dx.doi.org/10.1128/jvi.01439-15.

Full text

Abstract:

ABSTRACTThe propensity for transspecies prion transmission is related to the structural characteristics of the enciphering and new host PrP, although the exact mechanism remains incompletely understood. The effects of variability in prion protein on cross-species prion transmission have been studied with animal bioassays, but the influence of prion protein structure versus that of host cofactors (e.g., cellular constituents, trafficking, and innate immune interactions) remains difficult to dissect. To isolate the effects of protein-protein interactions on transspecies conversion, we used recombinant PrPCand real-time quaking-induced conversion (RT-QuIC) and compared chronic wasting disease (CWD) and classical bovine spongiform encephalopathy (cBSE) prions. To assess the impact of transmission to a new species, we studied feline CWD (fCWD) and feline BSE (i.e., feline spongiform encephalopathy [FSE]). We cross-seeded fCWD and FSE into each species' full-length, recombinant PrPCand measured the time required for conversion to the amyloid (PrPRes) form, which we describe here as the rate of amyloid conversion. These studies revealed the following: (i) CWD and BSE seeded their homologous species' PrP best; (ii) fCWD was a more efficient seed for feline rPrP than for white-tailed deer rPrP; (iii) conversely, FSE more efficiently converted bovine than feline rPrP; (iv) and CWD, fCWD, BSE, and FSE all converted human rPrP, although not as efficiently as homologous sCJD prions. These results suggest that (i) at the level of protein-protein interactions, CWD adapts to a new species more readily than does BSE and (ii) the barrier preventing transmission of CWD to humans may be less robust than estimated.IMPORTANCEWe demonstrate that bovine spongiform encephalopathy prions maintain their transspecies conversion characteristics upon passage to cats but that chronic wasting disease prions adapt to the cat and are distinguishable from the original prion. Additionally, we showed that chronic wasting disease prions are effective at seeding the conversion of normal human prion protein to an amyloid conformation, perhaps the first step in crossing the species barrier.

APA, Harvard, Vancouver, ISO, and other styles

17

Poggiolini, Ilaria, Daniela Saverioni, and Piero Parchi. "Prion Protein Misfolding, Strains, and Neurotoxicity: An Update from Studies on Mammalian Prions." International Journal of Cell Biology 2013 (2013): 1–24. http://dx.doi.org/10.1155/2013/910314.

Full text

Abstract:

Prion diseases, also known as transmissible spongiform encephalopathies (TSEs), are a group of fatal neurodegenerative disorders affecting humans and other mammalian species. The central event in TSE pathogenesis is the conformational conversion of the cellular prion protein,PrPC, into the aggregate,β-sheet rich, amyloidogenic form,PrPSc. Increasing evidence indicates that distinctPrPScconformers, forming distinct ordered aggregates, can encipher the phenotypic TSE variants related to prion strains. Prion strains are TSE isolates that, after inoculation into syngenic hosts, cause disease with distinct characteristics, such as incubation period, pattern ofPrPScdistribution, and regional severity of histopathological changes in the brain. In analogy with other amyloid forming proteins,PrPSctoxicity is thought to derive from the existence of various intermediate structures prior to the amyloid fiber formation and/or their specific interaction with membranes. The latter appears particularly relevant for the pathogenesis of TSEs associated with GPI-anchoredPrPSc, which involves major cellular membrane distortions in neurons. In this review, we update the current knowledge on the molecular mechanisms underlying three fundamental aspects of the basic biology of prions such as the putative mechanism of prion protein conversion to the pathogenic formPrPScand its propagation, the molecular basis of prion strains, and the mechanism of induced neurotoxicity byPrPScaggregates.

APA, Harvard, Vancouver, ISO, and other styles

18

Hara, Hideyuki, and Suehiro Sakaguchi. "N-Terminal Regions of Prion Protein: Functions and Roles in Prion Diseases." International Journal of Molecular Sciences 21, no. 17 (August 28, 2020): 6233. http://dx.doi.org/10.3390/ijms21176233.

Full text

Abstract:

The normal cellular isoform of prion protein, designated PrPC, is constitutively converted to the abnormally folded, amyloidogenic isoform, PrPSc, in prion diseases, which include Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy in animals. PrPC is a membrane glycoprotein consisting of the non-structural N-terminal domain and the globular C-terminal domain. During conversion of PrPC to PrPSc, its 2/3 C-terminal region undergoes marked structural changes, forming a protease-resistant structure. In contrast, the N-terminal region remains protease-sensitive in PrPSc. Reverse genetic studies using reconstituted PrPC-knockout mice with various mutant PrP molecules have revealed that the N-terminal domain has an important role in the normal function of PrPC and the conversion of PrPC to PrPSc. The N-terminal domain includes various characteristic regions, such as the positively charged residue-rich polybasic region, the octapeptide repeat (OR) region consisting of five repeats of an octapeptide sequence, and the post-OR region with another positively charged residue-rich polybasic region followed by a stretch of hydrophobic residues. We discuss the normal functions of PrPC, the conversion of PrPC to PrPSc, and the neurotoxicity of PrPSc by focusing on the roles of the N-terminal regions in these topics.

APA, Harvard, Vancouver, ISO, and other styles

19

Thapa, Simrika, Basant Abdulrahman, Dalia H. Abdelaziz, Li Lu, Manel Ben Aissa, and Hermann M. Schatzl. "Overexpression of quality control proteins reduces prion conversion in prion-infected cells." Journal of Biological Chemistry 293, no. 41 (August 28, 2018): 16069–82. http://dx.doi.org/10.1074/jbc.ra118.002754.

Full text

Abstract:

Prion diseases are fatal infectious neurodegenerative disorders in humans and other animals and are caused by misfolding of the cellular prion protein (PrPC) into the pathological isoform PrPSc. These diseases have the potential to transmit within or between species, including zoonotic transmission to humans. Elucidating the molecular and cellular mechanisms underlying prion propagation and transmission is therefore critical for developing molecular strategies for disease intervention. We have shown previously that impaired quality control mechanisms directly influence prion propagation. In this study, we manipulated cellular quality control pathways in vitro by stably and transiently overexpressing selected quality control folding (ERp57) and cargo (VIP36) proteins and investigated the effects of this overexpression on prion propagation. We found that ERp57 or VIP36 overexpression in persistently prion-infected neuroblastoma cells significantly reduces the amount of PrPSc in immunoblots and prion-seeding activity in the real-time quaking-induced conversion (RT-QuIC) assay. Using different cell lines infected with various prion strains confirmed that this effect is not cell type– or prion strain–specific. Moreover, de novo prion infection revealed that the overexpression significantly reduced newly formed PrPSc in acutely infected cells. ERp57-overexpressing cells significantly overcame endoplasmic reticulum stress, as revealed by expression of lower levels of the stress markers BiP and CHOP, accompanied by a decrease in PrP aggregates. Furthermore, application of ERp57-expressing lentiviruses prolonged the survival of prion-infected mice. Taken together, improved cellular quality control via ERp57 or VIP36 overexpression impairs prion propagation and could be utilized as a potential therapeutic strategy.

APA, Harvard, Vancouver, ISO, and other styles

20

Kazlauskaite, Jurate, and Teresa JT Pinheiro. "Binding of prion proteins to lipid membranes and implications for prion conversion." Biochemical Society Transactions 30, no. 3 (June 1, 2002): A95. http://dx.doi.org/10.1042/bst030a095b.

Full text

APA, Harvard, Vancouver, ISO, and other styles

21

Sanghera, Narinder, and Teresa J. T. Pinheiro. "Binding of prion protein to lipid membranes and implications for prion conversion." Journal of Molecular Biology 315, no. 5 (February 2002): 1241–56. http://dx.doi.org/10.1006/jmbi.2001.5322.

Full text

APA, Harvard, Vancouver, ISO, and other styles

22

Saleem, Fozia, Trent C. Bjorndahl, Carol L. Ladner, Rolando Perez-Pineiro, Burim N. Ametaj, and David S. Wishart. "Lipopolysaccharide induced conversion of recombinant prion protein." Prion 8, no. 2 (March 2014): 221–32. http://dx.doi.org/10.4161/pri.28939.

Full text

APA, Harvard, Vancouver, ISO, and other styles

23

Gill, Andrew C., Sonya Agarwal, Teresa J. T. Pinheiro, and James F. Graham. "Structural requirements for efficient prion protein conversion." Prion 4, no. 4 (October 2010): 235–43. http://dx.doi.org/10.4161/pri.4.4.13394.

Full text

APA, Harvard, Vancouver, ISO, and other styles

24

Carter, John, Audrius Zukas, Cathrin Bruederle, Audrius A. Zukas, Cathrin E. Bruederle, and John Mark Carter. "Sonication Induced Intermediate in Prion Protein Conversion." Protein & Peptide Letters 15, no. 2 (February 1, 2008): 206–11. http://dx.doi.org/10.2174/092986608783489517.

Full text

APA, Harvard, Vancouver, ISO, and other styles

25

Tuite, Mick F., and Tricia R. Serio. "Conformational conversion and prion disease: authors' reply." Nature Reviews Molecular Cell Biology 12, no. 4 (March 23, 2011): 273. http://dx.doi.org/10.1038/nrm3007-c2.

Full text

APA, Harvard, Vancouver, ISO, and other styles

26

Wang, Fei, Xinhe Wang, and Jiyan Ma. "Conversion of bacterially expressed recombinant prion protein." Methods 53, no. 3 (March 2011): 208–13. http://dx.doi.org/10.1016/j.ymeth.2010.12.013.

Full text

APA, Harvard, Vancouver, ISO, and other styles

27

Baral, Pravas, Mridula Swayampakula, Manoj Rout, Leo Spyracopoulos, Adriano Aguzzi, and Michael James. "Structural Basis of Prion Protein Conformation Conversion Inhibition." Acta Crystallographica Section A Foundations and Advances 70, a1 (August 5, 2014): C812. http://dx.doi.org/10.1107/s2053273314091876.

Full text

Abstract:

Prion diseases are fatal neurodegenerative diseases that affect humans and other animals. A conformational transition of the cellular prion protein, PrPC, into an infectious isoform, PrPSc, is the central event leading to aggregation and the fatal progression of these diseases. One of the therapeutic approaches for the prion diseases is the use of pharmacological chaperones. These molecules can stabilize the prion protein in its native conformation and can arrest the disease progression. Tricyclic phenothiazine compounds exhibit anti-prion activity; however, the underlying molecular mechanism of PrPSc inhibition remains elusive. We have determined the molecular structures of promazine and chlorpromazine bound to the mouse prion protein (moPrP) by forming crystals of the ternary complexes of the POM1 Fab:moPrP:promazine and the POM1 Fab:moPrP:chlorpromazine. The structures were solved by X-ray crystallography to resolutions of 1.9 Å and 2.2 Å, respectively. The small molecules are bound in a novel binding pocket formed at the intersection of the structured and the unstructured domains of the moPrP. Promazine binding induces a structural rearrangement of a portion of the unstructured region proximal to the first β-strand, β1, through the formation of a "hydrophobic anchor". We demonstrate that these molecules, promazine in particular, allosterically stabilize the misfolding initiator-motifs such as C-terminus of helix, α2, the α2-α3 loop as well as the polymorphic β2-α2 loop. Hence, the stabilization effects of the phenothiazine derivatives on initiator-motifs, induce a PrPC isoform that potentially resists oligomerization. Subtle structural differences are observed in the so-called initiator-motifs of the prion proteins that belong to many different mammalian species, and these diversities may possibly explain the generation of wide variety of scrapie strains in prion diseases.

APA, Harvard, Vancouver, ISO, and other styles

28

Barria, Marcelo A., Adriana Libori, Gordon Mitchell, and Mark W. Head. "Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions." Emerging Infectious Diseases 24, no. 8 (August 2018): 1482–89. http://dx.doi.org/10.3201/eid2408.161888.

Full text

APA, Harvard, Vancouver, ISO, and other styles

29

Caughey, Byron. "Prion protein interconversions†." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 356, no. 1406 (February 28, 2001): 197–202. http://dx.doi.org/10.1098/rstb.2000.0765.

Full text

Abstract:

The transmissible spongiform encephalopathies (TSEs), or prion diseases, remain mysterious neurodegenerative diseases that involve perturbations in prion protein (PrP) structure. This article summarizes our use of in vitro models to describe how PrP is converted to the disease–associated, protease–resistant form. These models reflect many important biological parameters of TSE diseases and have been used to identify inhibitors of the PrP conversion as lead compounds in the development of anti–TSE drugs.

APA, Harvard, Vancouver, ISO, and other styles

30

Rigter, Alan, and Alex Bossers. "Sheep scrapie susceptibility-linked polymorphisms do not modulate the initial binding of cellular to disease-associated prion protein prior to conversion." Journal of General Virology 86, no. 9 (September 1, 2005): 2627–34. http://dx.doi.org/10.1099/vir.0.80901-0.

Full text

Abstract:

Conversion of the host-encoded protease-sensitive cellular prion protein (PrPC) into the scrapie-associated protease-resistant isoform (PrPSc) of prion protein (PrP) is the central event in transmissible spongiform encephalopathies or prion diseases. Differences in transmissibility and susceptibility are largely determined by polymorphisms in PrP, but the exact molecular mechanism behind PrP conversion and the modulation by disease-associated polymorphisms is still unclear. To assess whether the polymorphisms in either PrPC or PrPSc modulate the initial binding of PrPC to PrPSc, several naturally occurring allelic variants of sheep PrPC and PrPSc that are associated with differential scrapie susceptibility and transmissibility [the phylogenetic wild-type (ARQ), the codon 136Val variant (VRQ) and the codon 171Arg variant (ARR)] were used. Under cell-free PrP conversion conditions known to reproduce the observed in vivo differential scrapie susceptibility, it was found that the relative amounts of PrPC allelic variants bound by various allelic PrPSc variants are PrP-specific and have comparable binding efficiencies. Therefore, the differential rate-limiting step in conversion of sheep PrP variants is not determined by the initial PrPC–PrPSc-binding efficiency, but seems to be an intrinsic property of PrPC itself. Consequently, a second step after PrPC–PrPSc-binding should determine the observed differences in PrP conversion efficiencies. Further study of this second step may provide a future tool to determine the mechanism underlying refolding of PrPC into PrPSc and supports the use of conversion-resistant polymorphic PrPC variants as a potential therapeutic approach to interfere with PrP conversion in transmissible spongiform encephalopathy development.

APA, Harvard, Vancouver, ISO, and other styles

31

Atarashi, Ryuichiro, Valerie L. Sim, Noriyuki Nishida, Byron Caughey, and Shigeru Katamine. "Prion Strain-Dependent Differences in Conversion of Mutant Prion Proteins in Cell Culture." Journal of Virology 80, no. 16 (August 15, 2006): 7854–62. http://dx.doi.org/10.1128/jvi.00424-06.

Full text

Abstract:

ABSTRACT Although the protein-only hypothesis proposes that it is the conformation of abnormal prion protein (PrPSc) that determines strain diversity, the molecular basis of strains remains to be elucidated. In the present study, we generated a series of mutations in the normal prion protein (PrPC) in which a single glutamine residue was replaced with a basic amino acid and compared their abilities to convert to PrPSc in cultured neuronal N2a58 cells infected with either the Chandler or 22L mouse-adapted scrapie strain. In mice, these strains generate PrPSc of the same sequence but different conformations, as judged by infrared spectroscopy. Substitutions at codons 97, 167, 171, and 216 generated PrPC that resisted conversion and inhibited the conversion of coexpressed wild-type PrP in both Chandler-infected and 22L-infected cells. Interestingly, substitutions at codons 185 and 218 gave strain-dependent effects. The Q185R and Q185K PrP were efficiently converted to PrPSc in Chandler-infected but not 22L-infected cells. Conversely, Q218R and Q218H PrP were converted only in 22L-infected cells. Moreover, the Q218K PrP exerted a potent inhibitory effect on the conversion of coexpressed wild-type PrP in Chandler-infected cells but had little effect on 22L-infected cells. These results show that two strains with the same PrP sequence but different conformations have differing abilities to convert the same mutated PrPC.

APA, Harvard, Vancouver, ISO, and other styles

32

Ma, Jiyan, Jingjing Zhang, and Runchuan Yan. "Recombinant Mammalian Prions: The “Correctly” Misfolded Prion Protein Conformers." Viruses 14, no. 9 (August 31, 2022): 1940. http://dx.doi.org/10.3390/v14091940.

Full text

Abstract:

Generating a prion with exogenously produced recombinant prion protein is widely accepted as the ultimate proof of the prion hypothesis. Over the years, a plethora of misfolded recPrP conformers have been generated, but despite their seeding capability, many of them have failed to elicit a fatal neurodegenerative disorder in wild-type animals like a naturally occurring prion. The application of the protein misfolding cyclic amplification technique and the inclusion of non-protein cofactors in the reaction mixture have led to the generation of authentic recombinant prions that fully recapitulate the characteristics of native prions. Together, these studies reveal that recPrP can stably exist in a variety of misfolded conformations and when inoculated into wild-type animals, misfolded recPrP conformers cause a wide range of outcomes, from being completely innocuous to lethal. Since all these recPrP conformers possess seeding capabilities, these results clearly suggest that seeding activity alone is not equivalent to prion activity. Instead, authentic prions are those PrP conformers that are not only heritable (the ability to seed the conversion of normal PrP) but also pathogenic (the ability to cause fatal neurodegeneration). The knowledge gained from the studies of the recombinant prion is important for us to understand the pathogenesis of prion disease and the roles of misfolded proteins in other neurodegenerative disorders.

APA, Harvard, Vancouver, ISO, and other styles

33

Krauss, Sybille, and Ina Vorberg. "PrionsEx Vivo: What Cell Culture Models Tell Us about Infectious Proteins." International Journal of Cell Biology 2013 (2013): 1–14. http://dx.doi.org/10.1155/2013/704546.

Full text

Abstract:

Prions are unconventional infectious agents that are composed of misfolded aggregated prion protein. Prions replicate their conformation by template-assisted conversion of the endogenous prion protein PrP. Templated conversion of soluble proteins into protein aggregates is also a hallmark of other neurodegenerative diseases. Alzheimer’s disease or Parkinson’s disease are not considered infectious diseases, although aggregate pathology appears to progress in a stereotypical fashion reminiscent of the spreading behavior ofmammalian prions. While basic principles of prion formation have been studied extensively, it is still unclear what exactly drives PrP molecules into an infectious, self-templating conformation. In this review, we discuss crucial steps in the life cycle of prions that have been revealed inex vivomodels. Importantly, the persistent propagation of prions in mitotically active cells argues that cellular processes are in place that not only allow recruitment of cellular PrP into growing prion aggregates but also enable the multiplication of infectious seeds that are transmitted to daughter cells. Comparison of prions with other protein aggregates demonstrates that not all the characteristics of prions are equally shared by prion-like aggregates. Future experiments may reveal to which extent aggregation-prone proteins associated with other neurodegenerative diseases can copy the replication strategies of prions.

APA, Harvard, Vancouver, ISO, and other styles

34

Atarashi, Ryuichiro, Roger A. Moore, Valerie L. Sim, Andrew G. Hughson, David W. Dorward, Henry A. Onwubiko, Suzette A. Priola, and Byron Caughey. "Ultrasensitive detection of scrapie prion protein using seeded conversion of recombinant prion protein." Nature Methods 4, no. 8 (July 22, 2007): 645–50. http://dx.doi.org/10.1038/nmeth1066.

Full text

APA, Harvard, Vancouver, ISO, and other styles

35

do Carmo Ferreira, Natália, and Byron Caughey. "Cell-free prion protein conversion assays in screening for anti-prion drug candidates." Current Opinion in Pharmacology 44 (February 2019): 1–7. http://dx.doi.org/10.1016/j.coph.2018.10.001.

Full text

APA, Harvard, Vancouver, ISO, and other styles

36

Kang, Hae-Eun, Jifeng Bian, Sarah J. Kane, Sehun Kim, Vanessa Selwyn, Jenna Crowell, Jason C. Bartz, and Glenn C. Telling. "Incomplete glycosylation during prion infection unmasks a prion protein epitope that facilitates prion detection and strain discrimination." Journal of Biological Chemistry 295, no. 30 (June 8, 2020): 10420–33. http://dx.doi.org/10.1074/jbc.ra120.012796.

Full text

Abstract:

The causative factors underlying conformational conversion of cellular prion protein (PrPC) into its infectious counterpart (PrPSc) during prion infection remain undetermined, in part because of a lack of monoclonal antibodies (mAbs) that can distinguish these conformational isoforms. Here we show that the anti-PrP mAb PRC7 recognizes an epitope that is shielded from detection when glycans are attached to Asn-196. We observed that whereas PrPC is predisposed to full glycosylation and is therefore refractory to PRC7 detection, prion infection leads to diminished PrPSc glycosylation at Asn-196, resulting in an unshielded PRC7 epitope that is amenable to mAb recognition upon renaturation. Detection of PRC7-reactive PrPSc in experimental and natural infections with various mouse-adapted scrapie strains and with prions causing deer and elk chronic wasting disease and transmissible mink encephalopathy uncovered that incomplete PrPSc glycosylation is a consistent feature of prion pathogenesis. We also show that interrogating the conformational properties of the PRC7 epitope affords a direct means of distinguishing different prion strains. Because the specificity of our approach for prion detection and strain discrimination relies on the extent to which N-linked glycosylation shields or unshields PrP epitopes from antibody recognition, it dispenses with the requirement for additional standard manipulations to distinguish PrPSc from PrPC, including evaluation of protease resistance. Our findings not only highlight an innovative and facile strategy for prion detection and strain differentiation, but are also consistent with a mechanism of prion replication in which structural instability of incompletely glycosylated PrP contributes to the conformational conversion of PrPC to PrPSc.

APA, Harvard, Vancouver, ISO, and other styles

37

McMahon, Hilary E. M. "Prion processing: a double-edged sword?" Biochemical Society Transactions 40, no. 4 (July 20, 2012): 735–38. http://dx.doi.org/10.1042/bst20120031.

Full text

Abstract:

The events leading to the degradation of the endogenous PrPC (normal cellular prion protein) have been the subject of numerous studies. Two cleavage processes, α-cleavage and β-cleavage, are responsible for the main C- and N-terminal fragments produced from PrPC. Both cleavage processes occur within the N-terminus of PrPC, a region that is significant in terms of function. α-Cleavage, an enzymatic event that occurs at amino acid residues 110 and 111 on PrPC, interferes with the conversion of PrPC into the prion disease-associated isoform, PrPSc (abnormal disease-specific conformation of prion protein). This processing is seen as a positive event in terms of disease development. The study of β-cleavage has taken some surprising turns. β-Cleavage is brought about by ROS (reactive oxygen species). The C-terminal fragment produced, C2, may provide the seed for the abnormal conversion process, as it resembles in size the fragments isolated from prion-infected brains. There is, however, strong evidence that β-cleavage provides an essential process to reduce oxidative stress. β-Cleavage may act as a double-edged sword. By β-cleavage, PrPC may try to balance the ROS levels produced during prion infection, but the C2 produced may provide a PrPSc seed that maintains the prion conversion process.

APA, Harvard, Vancouver, ISO, and other styles

38

Legname, Giuseppe. "Early structural features in mammalian prion conformation conversion." Prion 6, no. 1 (January 2012): 37–39. http://dx.doi.org/10.4161/pri.6.1.18425.

Full text

APA, Harvard, Vancouver, ISO, and other styles

39

Spagnolli, Giovanni, Marta Rigoli, Simone Orioli, Alejandro M. Sevillano, Pietro Faccioli, Holger Wille, Emiliano Biasini, and Jesús R. Requena. "Full atomistic model of prion structure and conversion." PLOS Pathogens 15, no. 7 (July 11, 2019): e1007864. http://dx.doi.org/10.1371/journal.ppat.1007864.

Full text

APA, Harvard, Vancouver, ISO, and other styles

40

Kudryavtseva, Sofia S., Aleksandra K. Melnikova, Vladimir I. Muronetz, and Yulia Yu Stroylova. "Methylglyoxal modification hinders amyloid conversion of prion protein." Mendeleev Communications 28, no. 3 (May 2018): 314–16. http://dx.doi.org/10.1016/j.mencom.2018.05.029.

Full text

APA, Harvard, Vancouver, ISO, and other styles

41

Head, Mark W., and James W. Ironside. "Inhibition of prion-protein conversion: a therapeutic tool?" Trends in Microbiology 8, no. 1 (January 2000): 6–8. http://dx.doi.org/10.1016/s0966-842x(99)01656-x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

42

Kuwata, K., N. Nishida, T. Matsumoto, Y. O. Kamatari, J. Hosokawa-Muto, K. Kodama, H. K. Nakamura, et al. "Hot spots in prion protein for pathogenic conversion." Proceedings of the National Academy of Sciences 104, no. 29 (July 6, 2007): 11921–26. http://dx.doi.org/10.1073/pnas.0702671104.

Full text

APA, Harvard, Vancouver, ISO, and other styles

43

Hooper, Nigel M. "Glypican-1 facilitates prion conversion in lipid rafts." Journal of Neurochemistry 116, no. 5 (February 9, 2011): 721–25. http://dx.doi.org/10.1111/j.1471-4159.2010.06936.x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

44

Marijanovic, Zrinka, Anna Caputo, Vincenza Campana, and Chiara Zurzolo. "Identification of an Intracellular Site of Prion Conversion." PLoS Pathogens 5, no. 5 (May 8, 2009): e1000426. http://dx.doi.org/10.1371/journal.ppat.1000426.

Full text

APA, Harvard, Vancouver, ISO, and other styles

45

Caughey, B., and G. S. Baron. "Factors affecting interactions between prion protein isoforms." Biochemical Society Transactions 30, no. 4 (August 1, 2002): 565–69. http://dx.doi.org/10.1042/bst0300565.

Full text

Abstract:

Interactions between normal, protease-sensitive prion protein (PrP-sen or PrPc) and its protease-resistant isoform (PrP-res or PrPsc) are critical in transmissible spongiform encephalopathy (TSE) diseases. To investigate the propagation of PrP-res between cells we tested whether PrP-res in scrapie brain microsomes can induce the conversion of PrP-sen to PrP-res if the PrP-sen is bound to uninfected raft membranes. Surprisingly, no conversion was observed unless the microsomal and raft membranes were fused or PrP-sen was released from raft membranes. These results suggest that the propagation of infection between cells requires transfer of PrP-res into the membranes of the recipient cell. To assess potential cofactors in PrP conversion, we used cell-free PrP conversion assays to show that heparan sulphate can stimulate PrP-res formation, supporting the idea that endogenous sulphated glycosaminoglycans can act as important cofactors or modulators of PrP-res formation in vivo. In an effort to develop therapeutics, the antimalarial drug quinacrine was identified as an inhibitor of PrP-res formation in scrapie-infected cell cultures. Confirmation of the latter result by others has led to the initiation of human clinical trials as a treatment for Creutzfeldt-Jakob disease. PrP-res formation can also be inhibited using a variety of other types of small molecule, specific synthetic PrP peptides, and an antiserum directed at the C-terminus of PrP-sen. The latter results help to localize the sites of interaction between PrP-sen and PrP-res. Disruption of those interactions with antibodies or peptidomimetic drugs may be an attractive therapeutic strategy. The likelihood that PrP-res inhibitors can rid TSE-infected tissues of PrP-res would presumably be enhanced if PrP-res formation were reversible. However, our attempts to measure dissociation of PrP-sen from PrP-res have failed under non-denaturing conditions. Finally, we have attempted to induce the spontaneous conversion of PrP-sen into PrP-res using low concentrations of detergents. A conformational conversion from α-helical monomers into high-β-sheet aggregates and fibrils was induced by low concentrations of the detergent sarkosyl; however, the aggregates had neither infectivity nor the characteristic protease-resistance of PrP-res.

APA, Harvard, Vancouver, ISO, and other styles

46

Orge, Leonor, Carla Lima, Carla Machado, Paula Tavares, Paula Mendonça, Paulo Carvalho, João Silva, et al. "Neuropathology of Animal Prion Diseases." Biomolecules 11, no. 3 (March 21, 2021): 466. http://dx.doi.org/10.3390/biom11030466.

Full text

Abstract:

Transmissible Spongiform Encephalopathies (TSEs) or prion diseases are a fatal group of infectious, inherited and spontaneous neurodegenerative diseases affecting human and animals. They are caused by the conversion of cellular prion protein (PrPC) into a misfolded pathological isoform (PrPSc or prion- proteinaceous infectious particle) that self-propagates by conformational conversion of PrPC. Yet by an unknown mechanism, PrPC can fold into different PrPSc conformers that may result in different prion strains that display specific disease phenotype (incubation time, clinical signs and lesion profile). Although the pathways for neurodegeneration as well as the involvement of brain inflammation in these diseases are not well understood, the spongiform changes, neuronal loss, gliosis and accumulation of PrPSc are the characteristic neuropathological lesions. Scrapie affecting small ruminants was the first identified TSE and has been considered the archetype of prion diseases, though atypical and new animal prion diseases continue to emerge highlighting the importance to investigate the lesion profile in naturally affected animals. In this report, we review the neuropathology and the neuroinflammation of animal prion diseases in natural hosts from scrapie, going through the zoonotic bovine spongiform encephalopathy (BSE), the chronic wasting disease (CWD) to the newly identified camel prion disease (CPD).

APA, Harvard, Vancouver, ISO, and other styles

47

Harris, David A. "Cellular Biology of Prion Diseases." Clinical Microbiology Reviews 12, no. 3 (July 1, 1999): 429–44. http://dx.doi.org/10.1128/cmr.12.3.429.

Full text

Abstract:

Prion diseases are fatal neurodegenerative disorders of humans and animals that are important because of their impact on public health and because they exemplify a novel mechanism of infectivity and biological information transfer. These diseases are caused by conformational conversion of a normal host glycoprotein (PrPC) into an infectious isoform (PrPSc) that is devoid of nucleic acid. This review focuses on the current understanding of prion diseases at the cell biological level. The characteristics of the diseases are introduced, and a brief history and description of the prion hypothesis are given. Information is then presented about the structure, expression, biosynthesis, and possible function of PrPC, as well as its posttranslational processing, cellular localization, and trafficking. The latest findings concerning PrPSc are then discussed, including cell culture systems used to generate this pathogenic isoform, the subcellular distribution of the protein, its membrane attachment, proteolytic processing, and its kinetics and sites of synthesis. Information is also provided on molecular models of the PrPC→PrPSc conversion reaction and the possible role of cellular chaperones. The review concludes with suggestions of several important avenues for future investigation.

APA, Harvard, Vancouver, ISO, and other styles

48

Delmouly, Karine, Maxime Belondrade, Danielle Casanova, Ollivier Milhavet, and Sylvain Lehmann. "HEPES inhibits the conversion of prion protein in cell culture." Journal of General Virology 92, no. 5 (May 1, 2011): 1244–50. http://dx.doi.org/10.1099/vir.0.027334-0.

Full text

Abstract:

HEPES is a well-known buffering reagent used in cell-culture medium. Interestingly, this compound is also responsible for significant modifications of biological parameters such as uptake of organic molecules, alteration of oxidative stress mechanisms or inhibition of ion channels. While using cell-culture medium supplemented with HEPES on prion-infected cells, it was noticed that there was a significant concentration-dependent inhibition of accumulation of the abnormal isoform of the prion protein (PrPSc). This effect was present only in live cells and was thought to be related to modification of the PrP environment or biology. These results could modify the interpretation of cell-culture assays of prion therapeutic agents, as well as of previous cell biology results obtained in the field using HEPES buffers. This inhibitory effect of HEPES could also be exploited to prevent contamination or propagation of prions in cell culture.

APA, Harvard, Vancouver, ISO, and other styles

49

Choi, Jin-Kyu, Ignazio Cali, Krystyna Surewicz, Qingzhong Kong, Pierluigi Gambetti, and Witold K. Surewicz. "Amyloid fibrils from the N-terminal prion protein fragment are infectious." Proceedings of the National Academy of Sciences 113, no. 48 (November 14, 2016): 13851–56. http://dx.doi.org/10.1073/pnas.1610716113.

Full text

Abstract:

Recombinant C-terminally truncated prion protein PrP23-144 (which corresponds to the Y145Stop PrP variant associated with a Gerstmann–Sträussler–Scheinker-like prion disease) spontaneously forms amyloid fibrils with a parallel in-register β-sheet architecture and β-sheet core mapping to residues ∼112–139. Here we report that mice (bothtga20and wild type) inoculated with a murine (moPrP23-144) version of these fibrils develop clinical prion disease with a 100% attack rate. Remarkably, even though fibrils in the inoculum lack the entire C-terminal domain of PrP, brains of clinically sick mice accumulate longer proteinase K-resistant (PrPres) fragments of ∼17–32 kDa, similar to those observed in classical scrapie strains. Shorter, Gerstmann–Sträussler–Scheinker-like PrPresfragments are also present. The evidence that moPrP23-144 amyloid fibrils generated in the absence of any cofactors are bona fide prions provides a strong support for the protein-only hypothesis of prion diseases in its pure form, arguing against the notion that nonproteinaceous cofactors are obligatory structural components of all infectious prions. Furthermore, our finding that a relatively short β-sheet core of PrP23-144 fibrils (residues ∼112–139) with a parallel in-register organization of β-strands is capable of seeding the conversion of full-length prion protein to the infectious form has important implications for the ongoing debate regarding structural aspects of prion protein conversion and molecular architecture of mammalian prions.

APA, Harvard, Vancouver, ISO, and other styles

50

Hannaoui, Samia, Sara Amidian, Yo Ching Cheng, Camilo Duque Velásquez, Lyudmyla Dorosh, Sampson Law, Glenn Telling, et al. "Destabilizing polymorphism in cervid prion protein hydrophobic core determines prion conformation and conversion efficiency." PLOS Pathogens 13, no. 8 (August 11, 2017): e1006553. http://dx.doi.org/10.1371/journal.ppat.1006553.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Journal articles on the topic 'Prion conversion'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles