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Science 9 April 1982:
Vol. 216. no. 4542, pp. 136 - 144
DOI: 10.1126/science.6801762

Articles

Science, Vol 216, Issue 4542, 136-144
Copyright © 1982 by American Association for the Advancement of Science


articles

Novel proteinaceous infectious particles cause scrapie

SB Prusiner

After infection and a prolonged incubation period, the scrapie agent causes a degenerative disease of the central nervous system in sheep and goats. Six lines of evidence including sensitivity to proteases demonstrate that this agent contains a protein that is required for infectivity. Although the scrapie agent is irreversibly inactivated by alkali, five procedures with more specificity for modifying nucleic acids failed to cause inactivation. The agent shows heterogeneity with respect to size, apparently a result of its hydrophobicity; the smallest form may have a molecular weight of 50,000 or less. Because the novel properties of the scrapie agent distinguish it from viruses, plasmids, and viroids, a new term "prion" is proposed to denote a small proteinaceous infectious particle which is resistant to inactivation by most procedures that modify nucleic acids. Knowledge of the scrapie agent structure may have significance for understanding the causes of several degenerative diseases.


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Regulation of Prion Gene Expression by Transcription Factors SP1 and Metal Transcription Factor-1.
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Identifying Key Components of the PrPC-PrPSc Replicative Interface.
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J. Biol. Chem. 283, 34021-34028
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Association of a null allele of SPRN with variant Creutzfeldt-Jakob disease.
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The changing face of kuru: a personal perspective.
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Molecular and Transmission Characteristics of Primary-Passaged Ovine Scrapie Isolates in Conventional and Ovine PrP Transgenic Mice.
A. M. Thackray, L. Hopkins, J. Spiropoulos, and R. Bujdoso (2008)
J. Virol. 82, 11197-11207
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Small-Ruminant Lentivirus Enhances PrPSc Accumulation in Cultured Sheep Microglial Cells.
J. B. Stanton, D. P. Knowles, K. I. O'Rourke, L. M. Herrmann-Hoesing, B. A. Mathison, and T. V. Baszler (2008)
J. Virol. 82, 9839-9847
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The effects of prion protein proteolysis and disaggregation on the strain properties of hamster scrapie.
A. M. Deleault, N. R. Deleault, B. T. Harris, J. R. Rees, and S. Supattapone (2008)
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Amyloid Fibrils of the HET-s(218-289) Prion Form a {beta} Solenoid with a Triangular Hydrophobic Core.
C. Wasmer, A. Lange, H. Van Melckebeke, A. B. Siemer, R. Riek, and B. H. Meier (2008)
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The elk PRNP codon 132 polymorphism controls cervid and scrapie prion propagation.
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Protein Misfolding and Neurodegeneration.
C. Soto and L. D. Estrada (2008)
Arch Neurol 65, 184-189
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Unraveling prion strains with cell biology and organic chemistry.
A. Aguzzi (2008)
PNAS 105, 11-12
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Decontamination of surgical instruments from prions. II. In vivo findings with a model system for testing the removal of scrapie infectivity from steel surfaces.
K. Lemmer, M. Mielke, C. Kratzel, M. Joncic, M. Oezel, G. Pauli, and M. Beekes (2008)
J. Gen. Virol. 89, 348-358
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Selective Incorporation of Polyanionic Molecules into Hamster Prions.
J. C. Geoghegan, P. A. Valdes, N. R. Orem, N. R. Deleault, R. A. Williamson, B. T. Harris, and S. Supattapone (2007)
J. Biol. Chem. 282, 36341-36353
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Influence of Water, Fat, and Glycerol on the Mechanism of Thermal Prion Inactivation.
H. Muller, L. Stitz, H. Wille, S. B. Prusiner, and D. Riesner (2007)
J. Biol. Chem. 282, 35855-35867
   Abstract »    Full Text »    PDF »
High Titers of Transmissible Spongiform Encephalopathy Infectivity Associated with Extremely Low Levels of PrPSc in Vivo.
R. M. Barron, S. L. Campbell, D. King, A. Bellon, K. E. Chapman, R. A. Williamson, and J. C. Manson (2007)
J. Biol. Chem. 282, 35878-35886
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Medical Mineralogy and Geochemistry: An Interfacial Science.
N. Sahai (2007)
Elements 3, 381-384
   Abstract »    Full Text »    PDF »
Role of Hsp104 in the Propagation and Inheritance of the [Het-s] Prion.
L. Malato, S. Dos Reis, L. Benkemoun, R. Sabate, and S. J. Saupe (2007)
Mol. Biol. Cell 18, 4803-4812
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Molecular architecture of human prion protein amyloid: A parallel, in-register -structure.
N. J. Cobb, F. D. Sonnichsen, H. Mchaourab, and W. K. Surewicz (2007)
PNAS 104, 18946-18951
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Molecular Characterization of the Rocky Mountain Elk (Cervus elaphus nelsoni) PRNP Putative Promoter.
C. M. Seabury, C. A. Gill, J. W. Templeton, J. B. Dyar, J. N. Derr, D. L. Adelson, E. Owens, D. S. Davis, D. C. Kraemer, and J. E. Womack (2007)
J. Hered.
   Abstract »    Full Text »    PDF »
Mouse-Adapted Ovine Scrapie Prion Strains Are Characterized by Different Conformers of PrPSc.
A. M. Thackray, L. Hopkins, M. A. Klein, and R. Bujdoso (2007)
J. Virol. 81, 12119-12127
   Abstract »    Full Text »    PDF »
A General Model of Prion Strains and Their Pathogenicity.
J. Collinge and A. R. Clarke (2007)
Science 318, 930-936
   Abstract »    Full Text »    PDF »
PrPc Does Not Mediate Internalization of PrPSc but Is Required at an Early Stage for De Novo Prion Infection of Rov Cells.
S. Paquet, N. Daude, M.-P. Courageot, J. Chapuis, H. Laude, and D. Vilette (2007)
J. Virol. 81, 10786-10791
   Abstract »    Full Text »    PDF »
Polylactide-Coglycolide Microspheres CoEncapsulating Recombinant Tandem Prion Protein with CpG-Oligonucleotide Break Self-Tolerance to Prion Protein in Wild-Type Mice and Induce CD4 and CD8 T Cell Responses.
G. Kaiser-Schulz, A. Heit, L. Quintanilla-Martinez, F. Hammerschmidt, S. Hess, L. Jennen, H. Rezaei, H. Wagner, and H. M. Schatzl (2007)
J. Immunol. 179, 2797-2807
   Abstract »    Full Text »    PDF »
Species-specific Differences in the Intermediate States of Human and Syrian Hamster Prion Protein Detected by High Pressure NMR Spectroscopy.
W. Kremer, N. Kachel, K. Kuwata, K. Akasaka, and H. R. Kalbitzer (2007)
J. Biol. Chem. 282, 22689-22698
   Abstract »    Full Text »    PDF »
Hot spots in prion protein for pathogenic conversion.
K. Kuwata, N. Nishida, T. Matsumoto, Y. O. Kamatari, J. Hosokawa-Muto, K. Kodama, H. K. Nakamura, K. Kimura, M. Kawasaki, Y. Takakura, et al. (2007)
PNAS 104, 11921-11926
   Abstract »    Full Text »    PDF »
From the Cover: Formation of native prions from minimal components in vitro.
N. R. Deleault, B. T. Harris, J. R. Rees, and S. Supattapone (2007)
PNAS 104, 9741-9746
   Abstract »    Full Text »    PDF »
PrPSc in Salivary Glands of Scrapie-Affected Sheep.
M. Vascellari, R. Nonno, F. Mutinelli, M. Bigolaro, M. A. Di Bari, E. Melchiotti, S. Marcon, C. D'Agostino, G. Vaccari, M. Conte, et al. (2007)
J. Virol. 81, 4872-4876
   Abstract »    Full Text »    PDF »
Resistance to Chronic Wasting Disease in Transgenic Mice Expressing a Naturally Occurring Allelic Variant of Deer Prion Protein.
K. Meade-White, B. Race, M. Trifilo, A. Bossers, C. Favara, R. Lacasse, M. Miller, E. Williams, M. Oldstone, R. Race, et al. (2007)
J. Virol. 81, 4533-4539
   Abstract »    Full Text »    PDF »
Diversity in prion protein oligomerization pathways results from domain expansion as revealed by hydrogen/deuterium exchange and disulfide linkage.
F. Eghiaian, T. Daubenfeld, Y. Quenet, M. van Audenhaege, A.-P. Bouin, G. van der Rest, J. Grosclaude, and H. Rezaei (2007)
PNAS 104, 7414-7419
   Abstract »    Full Text »    PDF »
Human prion proteins with pathogenic mutations share common conformational changes resulting in enhanced binding to glycosaminoglycans.
S. Yin, N. Pham, S. Yu, C. Li, P. Wong, B. Chang, S.-C. Kang, E. Biasini, P. Tien, D. A. Harris, et al. (2007)
PNAS 104, 7546-7551
   Abstract »    Full Text »    PDF »
Polymorphisms of the prion protein gene coding region in born-after-the-reinforced-ban (BARB) bovine spongiform encephalopathy cattle in Great Britain.
G. C. Saunders, P. C. Griffiths, S. Cawthraw, A. C. Tout, P. Wiener, J. A. Woolliams, J. L. Williams, and O. Windl (2007)
J. Gen. Virol. 88, 1374-1378
   Abstract »    Full Text »    PDF »
Immunological differences between susceptible and resistant sheep during the preclinical phase of scrapie infection.
S. L. Eaton, M. Rocchi, L. Gonzalez, S. Hamilton, J. Finlayson, J. Sales, M. Jeffrey, P. J. Steele, M. P. Dagleish, S. M. Rodger, et al. (2007)
J. Gen. Virol. 88, 1384-1391
   Abstract »    Full Text »    PDF »
In Vitro Analysis of SpUre2p, a Prion-related Protein, Exemplifies the Relationship between Amyloid and Prion.
F. Immel, Y. Jiang, Y.-Q. Wang, C. Marchal, L. Maillet, S. Perrett, and C. Cullin (2007)
J. Biol. Chem. 282, 7912-7920
   Abstract »    Full Text »    PDF »
Oligomerization of the Human Prion Protein Proceeds via a Molten Globule Intermediate.
R. Gerber, A. Tahiri-Alaoui, P. J. Hore, and W. James (2007)
J. Biol. Chem. 282, 6300-6307
   Abstract »    Full Text »    PDF »
Dynamics and genetics of PrPSc placental accumulation in sheep.
C. Lacroux, F. Corbiere, G. Tabouret, S. Lugan, P. Costes, J. Mathey, J. M. Delmas, J. L. Weisbecker, G. Foucras, H. Cassard, et al. (2007)
J. Gen. Virol. 88, 1056-1061
   Abstract »    Full Text »    PDF »
Microglial Cell Line Established from Prion Protein-Overexpressing Mice Is Susceptible to Various Murine Prion Strains.
Y. Iwamaru, T. Takenouchi, K. Ogihara, M. Hoshino, M. Takata, M. Imamura, Y. Tagawa, H. Hayashi-Kato, Y. Ushiki-Kaku, Y. Shimizu, et al. (2007)
J. Virol. 81, 1524-1527
   Abstract »    Full Text »    PDF »
Importance of the Hsp70 ATPase Domain in Yeast Prion Propagation.
H. M. Loovers, E. Guinan, and G. W. Jones (2007)
Genetics 175, 621-630
   Abstract »    Full Text »    PDF »
beta-Sheet core of human prion protein amyloid fibrils as determined by hydrogen/deuterium exchange.
X. Lu, P. L. Wintrode, and W. K. Surewicz (2007)
PNAS 104, 1510-1515
   Abstract »    Full Text »    PDF »
Prion Interference Is Due to a Reduction in Strain-Specific PrPSc Levels.
J. C. Bartz, M. L. Kramer, M. H. Sheehan, J. A. L. Hutter, J. I. Ayers, R. A. Bessen, and A. E. Kincaid (2007)
J. Virol. 81, 689-697
   Abstract »    Full Text »    PDF »
Test for Detection of Disease-Associated Prion Aggregate in the Blood of Infected but Asymptomatic Animals.
B. Chang, X. Cheng, S. Yin, T. Pan, H. Zhang, P. Wong, S.-C. Kang, F. Xiao, H. Yan, C. Li, et al. (2007)
Clin. Vaccine Immunol. 14, 36-43
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Prion infectivity in variant Creutzfeldt-Jakob disease rectum.
J D F Wadsworth, S Joiner, K Fox, J M Linehan, M Desbruslais, S Brandner, E A Asante, and J Collinge (2007)
Gut 56, 90-94
   Abstract »    Full Text »    PDF »
Strain Fidelity of Chronic Wasting Disease upon Murine Adaptation.
C. J. Sigurdson, G. Manco, P. Schwarz, P. Liberski, E. A. Hoover, S. Hornemann, M. Polymenidou, M. W. Miller, M. Glatzel, and A. Aguzzi (2006)
J. Virol. 80, 12303-12311
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Transmission and characterization of bovine spongiform encephalopathy sources in two ovine transgenic mouse lines (TgOvPrP4 and TgOvPrP59).
C. Cordier, A. Bencsik, S. Philippe, D. Betemps, F. Ronzon, D. Calavas, C. Crozet, and T. Baron (2006)
J. Gen. Virol. 87, 3763-3771
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Accelerated Accumulation of Misfolded Prion Protein and Spongiform Degeneration in a Drosophila Model of Gerstmann-Straussler-Scheinker Syndrome.
B. A. Gavin, M. J. Dolph, N. R. Deleault, J. C. Geoghegan, V. Khurana, M. B. Feany, P. J. Dolph, and S. Supattapone (2006)
J. Neurosci. 26, 12408-12414
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Ultra-efficient Replication of Infectious Prions by Automated Protein Misfolding Cyclic Amplification.
P. Saa, J. Castilla, and C. Soto (2006)
J. Biol. Chem. 281, 35245-35252
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Junctional expression of the prion protein PrPC by brain endothelial cells: a role in trans-endothelial migration of human monocytes.
P. Viegas, N. Chaverot, H. Enslen, N. Perriere, P.-O. Couraud, and S. Cazaubon (2006)
J. Cell Sci. 119, 4634-4643
   Abstract »    Full Text »    PDF »
Early and Rapid Engraftment of Bone Marrow-Derived Microglia in Scrapie..
J. Priller, M. Prinz, M. Heikenwalder, N. Zeller, P. Schwarz, F. L. Heppner, and A. Aguzzi (2006)
J. Neurosci. 26, 11753-11762
   Abstract »    Full Text »    PDF »
PrP genotypes of atypical scrapie cases in Great Britain..
G. C. Saunders, S. Cawthraw, S. J. Mountjoy, J. Hope, and O. Windl (2006)
J. Gen. Virol. 87, 3141-3149
   Abstract »    Full Text »    PDF »
Cell-free formation of misfolded prion protein with authentic prion infectivity.
P. Weber, A. Giese, N. Piening, G. Mitteregger, A. Thomzig, M. Beekes, and H. A. Kretzschmar (2006)
PNAS 103, 15818-15823
   Abstract »    Full Text »    PDF »
Prion diseases in humans: an update.
R. BUTLER (2006)
The British Journal of Psychiatry 189, 295-296
   Abstract »    Full Text »    PDF »
A systematic review of prion therapeutics in experimental models.
C. R Trevitt and J. Collinge (2006)
Brain 129, 2241-2265
   Abstract »    Full Text »    PDF »
Codon 129 polymorphism of the human prion protein influences the kinetics of amyloid formation..
P. A. Lewis, M. H. Tattum, S. Jones, D. Bhelt, M. Batchelor, A. R. Clarke, J. Collinge, and G. S. Jackson (2006)
J. Gen. Virol. 87, 2443-2449
   Abstract »    Full Text »    PDF »
Cross-Talk between RNA and Prions.
C. G. Crist and Y. Nakamura (2006)
J. Biochem. 140, 167-173
   Abstract »    Full Text »    PDF »
Prion-induced amyloid heart disease with high blood infectivity in transgenic mice..
M. J. Trifilo, T. Yajima, Y. Gu, N. Dalton, K. L. Peterson, R. E. Race, K. Meade-White, J. L. Portis, E. Masliah, K. U. Knowlton, et al. (2006)
Science 313, 94-97
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Childhood Onset in Familial Prion Disease With a Novel Mutation in the PRNP Gene..
E. Rogaeva, C. Zadikoff, J. Ponesse, G. Schmitt-Ulms, T. Kawarai, C. Sato, S. Salehi-Rad, P. St. George-Hyslop, and A. E. Lang (2006)
Arch Neurol 63, 1016-1021
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Acid inactivation of prions: efficient at elevated temperature or high acid concentration..
T. R. Appel, R. Lucassen, M. H. Groschup, M. Joncic, M. Beekes, and D. Riesner (2006)
J. Gen. Virol. 87, 1385-1394
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Prion Proteins with Insertion Mutations Have Altered N-terminal Conformation and Increased Ligand Binding Activity and Are More Susceptible to Oxidative Attack.
S. Yin, S. Yu, C. Li, P. Wong, B. Chang, F. Xiao, S.-C. Kang, H. Yan, G. Xiao, J. Grassi, et al. (2006)
J. Biol. Chem. 281, 10698-10705
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Conversion Efficiency of Bank Vole Prion Protein in Vitro Is Determined by Residues 155 and 170, but Does Not Correlate with the High Susceptibility of Bank Voles to Sheep Scrapie in Vivo.
N. Piening, R. Nonno, M. Di Bari, S. Walter, O. Windl, U. Agrimi, H. A. Kretzschmar, and U. Bertsch (2006)
J. Biol. Chem. 281, 9373-9384
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Functional disruption of the prion protein gene in cloned goats..
G. Yu, J. Chen, H. Yu, S. Liu, J. Chen, X. Xu, H. Sha, X. Zhang, G. Wu, S. Xu, et al. (2006)
J. Gen. Virol. 87, 1019-1027
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Characterization and Application of a Novel RNA Aptamer against the Mouse Prion Protein..
S. Sekiya, K. Noda, F. Nishikawa, T. Yokoyama, P. K.R. Kumar, and S. Nishikawa (2006)
J. Biochem. 139, 383-390
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Atypical prion protein in sheep brain collected during the British scrapie-surveillance programme.
S. J. Everest, L. Thorne, D. A. Barnicle, J. C. Edwards, H. Elliott, R. Jackman, and J. Hope (2006)
J. Gen. Virol. 87, 471-477
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Inactivation of Prions by Acidic Sodium Dodecyl Sulfate.
D. Peretz, S. Supattapone, K. Giles, J. Vergara, Y. Freyman, P. Lessard, J. G. Safar, D. V. Glidden, C. McCulloch, H.-O. B. Nguyen, et al. (2006)
J. Virol. 80, 322-331
   Abstract »    Full Text »    PDF »
Potential Role of Soil in the Transmission of Prion Disease.
P. T. Schramm, C. J. Johnson, N. E. Mathews, D. McKenzie, J. M. Aiken, and J. A. Pedersen (2006)
Reviews in Mineralogy and Geochemistry 64, 135-152
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Disease-related Prion Protein Forms Aggresomes in Neuronal Cells Leading to Caspase Activation and Apoptosis.
M. Kristiansen, M. J. Messenger, P.-C. Klohn, S. Brandner, J. D. F. Wadsworth, J. Collinge, and S. J. Tabrizi (2005)
J. Biol. Chem. 280, 38851-38861
   Abstract »    Full Text »    PDF »
A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes.
A. Le Dur, V. Beringue, O. Andreoletti, F. Reine, T. L. Lai, T. Baron, B. Bratberg, J.-L. Vilotte, P. Sarradin, S. L. Benestad, et al. (2005)
PNAS 102, 16031-16036
   Abstract »    Full Text »    PDF »
Neurochemical Insights.
C. Treiber (2005)
Sci. Aging Knowl. Environ. 2005, pe32
   Abstract »    Full Text »
Coincident Scrapie Infection and Nephritis Lead to Urinary Prion Excretion.
H. Seeger, M. Heikenwalder, N. Zeller, J. Kranich, P. Schwarz, A. Gaspert, B. Seifert, G. Miele, and A. Aguzzi (2005)
Science 310, 324-326
   Abstract »    Full Text »    PDF »
An Aggregation-Specific Enzyme-Linked Immunosorbent Assay: Detection of Conformational Differences between Recombinant PrP Protein Dimers and PrPSc Aggregates.
T. Pan, B. Chang, P. Wong, C. Li, R. Li, S.-C. Kang, J. D. Robinson, A. R. Thompsett, P. Tein, S. Yin, et al. (2005)
J. Virol. 79, 12355-12364
   Abstract »    Full Text »    PDF »
Interleukin 4 and Interleukin 10 Levels Are Elevated in the Cerebrospinal Fluid of Patients With Creutzfeldt-Jakob Disease.
K. Stoeck, M. Bodemer, B. Ciesielczyk, B. Meissner, M. Bartl, U. Heinemann, and I. Zerr (2005)
Arch Neurol 62, 1591-1594
   Abstract »    Full Text »    PDF »
The [URE3] Prion Is Not Conserved Among Saccharomyces Species.
N. Talarek, L. Maillet, C. Cullin, and M. Aigle (2005)
Genetics 171, 23-34
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Immunoquantitative PCR for Prion Protein Detection in Sporadic Creutzfeldt-Jakob Disease.
S. Gofflot, M. Deprez, B. el Moualij, A. Osman, J.-F. Thonnart, O. Hougrand, E. Heinen, and W. Zorzi (2005)
Clin. Chem. 51, 1605-1611
   Abstract »    Full Text »    PDF »
Search for a Prion-Specific Nucleic Acid.
J. G. Safar, K. Kellings, A. Serban, D. Groth, J. E. Cleaver, S. B. Prusiner, and D. Riesner (2005)
J. Virol. 79, 10796-10806
   Abstract »    Full Text »    PDF »
The prion gene is associated with human long-term memory.
A. Papassotiropoulos, M. A. Wollmer, A. Aguzzi, C. Hock, R. M. Nitsch, and D. J.-F. de Quervain (2005)
Hum. Mol. Genet. 14, 2241-2246
   Abstract »    Full Text »    PDF »
Protease-resistant Prion Protein Amplification Reconstituted with Partially Purified Substrates and Synthetic Polyanions.
N. R. Deleault, J. C. Geoghegan, K. Nishina, R. Kascsak, R. A. Williamson, and S. Supattapone (2005)
J. Biol. Chem. 280, 26873-26879
   Abstract »    Full Text »    PDF »
Molecular neurology of prion disease.
J Collinge (2005)
J. Neurol. Neurosurg. Psychiatry 76, 906-919
   Abstract »    Full Text »    PDF »



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