prpc proteins


Summary: Normal cellular isoform of PRION PROTEINS encoded by a chromosomal gene and found in normal and scrapie-infected brain tissue, and other normal tissue. PrPC are protease-sensitive proteins whose function is unknown. Posttranslational modification of PrPC into PrPSC leads to infectivity.

Top Publications

  1. Balducci C, Beeg M, Stravalaci M, Bastone A, Sclip A, Biasini E, et al. Synthetic amyloid-beta oligomers impair long-term memory independently of cellular prion protein. Proc Natl Acad Sci U S A. 2010;107:2295-300 pubmed publisher
    ..However, PrP-expressing and PrP knock-out mice were equally susceptible to this impairment. These data suggest that Abeta(1-42) oligomers are responsible for cognitive impairment in AD and that PrP(C) is not required. ..
  2. Brouckova A, Holada K. Cellular prion protein in blood platelets associates with both lipid rafts and the cytoskeleton. Thromb Haemost. 2009;102:966-74 pubmed publisher
    ..This localisation places PrPc in a position where it can interact with proteins involved in platelet signalling and eventually with vCJD prions. ..
  3. Resenberger U, Harmeier A, Woerner A, Goodman J, Muller V, Krishnan R, et al. The cellular prion protein mediates neurotoxic signalling of ?-sheet-rich conformers independent of prion replication. EMBO J. 2011;30:2057-70 pubmed publisher
    ..Our study indicates that PrP(C) can mediate toxic signalling of various ?-sheet-rich conformers independent of infectious prion propagation, suggesting a pathophysiological role of the prion protein beyond of prion diseases. ..
  4. Daude N, Wohlgemuth S, Rogaeva E, Farid A, Heaton M, Westaway D. Frequent missense and insertion/deletion polymorphisms in the ovine Shadoo gene parallel species-specific variation in PrP. PLoS ONE. 2009;4:e6538 pubmed publisher
    ..Frequent coding polymorphisms are a hallmark of the sheep PRNP gene and our data indicate a similar situation applies to ovine SPRN. Whether a common selection pressure balances diversity at both loci remains to be established. ..
  5. Daude N, Ng V, Watts J, Genovesi S, Glaves J, Wohlgemuth S, et al. Wild-type Shadoo proteins convert to amyloid-like forms under native conditions. J Neurochem. 2010;113:92-104 pubmed publisher
    ..Our studies define a proteinase K -resistant signature fragment for the amyloid fold of Sho and raise the question of a physiological role for this form of the wt protein. ..
  6. Ghaemmaghami S, Ullman J, Ahn M, St Martin S, Prusiner S. Chemical induction of misfolded prion protein conformers in cell culture. J Biol Chem. 2010;285:10415-23 pubmed publisher
    ..It remains to be established whether the formation of PrP(A) inhibits the formation of rPrP(Sc) by sequestering PrP(C) in the form of benign, insoluble aggregates. ..
  7. Almeida L, Basu U, Khaniya B, Taniguchi M, Williams J, Moore S, et al. Gene expression in the medulla following oral infection of cattle with bovine spongiform encephalopathy. J Toxicol Environ Health A. 2011;74:110-26 pubmed publisher
    ..Additional studies on larger number of animals are in progress in our laboratory to investigate the roles of these DE genes in pathogenesis of BSE. ..
  8. Geoghegan J, Miller M, Kwak A, Harris B, Supattapone S. Trans-dominant inhibition of prion propagation in vitro is not mediated by an accessory cofactor. PLoS Pathog. 2009;5:e1000535 pubmed publisher
  9. O Sullivan D, Jones C, Abdelraheim S, Brazier M, Toms H, Brown D, et al. Dynamics of a truncated prion protein, PrP(113-231), from (15)N NMR relaxation: order parameters calculated and slow conformational fluctuations localized to a distinct region. Protein Sci. 2009;18:410-23 pubmed publisher
    ..The flexibility within these residues could facilitate the PrP(C)-PrP(Sc) recognition process during fibril elongation. ..

More Information


  1. Liang J, Wang W, Sorensen D, Medina S, Ilchenko S, Kiselar J, et al. Cellular prion protein regulates its own ?-cleavage through ADAM8 in skeletal muscle. J Biol Chem. 2012;287:16510-20 pubmed publisher
    ..Moreover, we found that overexpression of PrP(C) led to up-regulation of ADAM8, suggesting that PrP(C) may regulate its own ?-cleavage through modulating ADAM8 activity. ..
  2. Gunther E, Strittmatter S. Beta-amyloid oligomers and cellular prion protein in Alzheimer's disease. J Mol Med (Berl). 2010;88:331-8 pubmed publisher
    ..Here, we review the importance of A beta oligomers in AD, commonalities between AD and CJD, and the newly emergent role of PrP(C) as a receptor for A beta oligomers. ..
  3. Spevacek A, Evans E, Miller J, Meyer H, Pelton J, Millhauser G. Zinc drives a tertiary fold in the prion protein with familial disease mutation sites at the interface. Structure. 2013;21:236-46 pubmed publisher
    ..The structural features identified here suggest mechanisms by which physiologic metal ions trigger PrP(C) trafficking and control prion disease. ..
  4. Pushie M, Pickering I, Martin G, Tsutsui S, Jirik F, George G. Prion protein expression level alters regional copper, iron and zinc content in the mouse brain. Metallomics. 2011;3:206-14 pubmed publisher
  5. Biscaro B, Lindvall O, Hock C, Ekdahl C, Nitsch R. Abeta immunotherapy protects morphology and survival of adult-born neurons in doubly transgenic APP/PS1 mice. J Neurosci. 2009;29:14108-19 pubmed publisher
  6. Um J, Nygaard H, Heiss J, Kostylev M, Stagi M, Vortmeyer A, et al. Alzheimer amyloid-? oligomer bound to postsynaptic prion protein activates Fyn to impair neurons. Nat Neurosci. 2012;15:1227-35 pubmed publisher
    ..These results delineate an A? oligomer signal transduction pathway that requires PrP(C) and Fyn to alter synaptic function, with deleterious consequences in Alzheimer's disease. ..
  7. Watts J, Huo H, Bai Y, Ehsani S, Jeon A, Won A, et al. Interactome analyses identify ties of PrP and its mammalian paralogs to oligomannosidic N-glycans and endoplasmic reticulum-derived chaperones. PLoS Pathog. 2009;5:e1000608 pubmed publisher
  8. Lewis V, Hill A, Haigh C, Klug G, Masters C, Lawson V, et al. Increased proportions of C1 truncated prion protein protect against cellular M1000 prion infection. J Neuropathol Exp Neurol. 2009;68:1125-35 pubmed publisher
  9. Cisse M, Duplan E, Guillot Sestier M, Rumigny J, Bauer C, Pages G, et al. The extracellular regulated kinase-1 (ERK1) controls regulated alpha-secretase-mediated processing, promoter transactivation, and mRNA levels of the cellular prion protein. J Biol Chem. 2011;286:29192-206 pubmed publisher
    ..Altogether, our data identify ERK1 as an important regulator of PrP(c) cellular homeostasis and indicate that this kinase exerts a dual control of PrP(c) levels through transcriptional and post-transcriptional mechanisms. ..
  10. Beraldo F, Arantes C, Santos T, Machado C, Roffe M, Hajj G, et al. Metabotropic glutamate receptors transduce signals for neurite outgrowth after binding of the prion protein to laminin ?1 chain. FASEB J. 2011;25:265-79 pubmed publisher
  11. Daude N, Wohlgemuth S, Brown R, Pitstick R, Gapeshina H, Yang J, et al. Knockout of the prion protein (PrP)-like Sprn gene does not produce embryonic lethality in combination with PrP(C)-deficiency. Proc Natl Acad Sci U S A. 2012;109:9035-40 pubmed publisher
    ..Alternatively, and in accord with some reports for PrP(C), we infer that Sho's activity will prove germane to the maintenance of neuronal viability in postnatal life. ..
  12. Le Pichon C, Valley M, Polymenidou M, Chesler A, Sagdullaev B, Aguzzi A, et al. Olfactory behavior and physiology are disrupted in prion protein knockout mice. Nat Neurosci. 2009;12:60-9 pubmed publisher
    ..These data suggest that PrP(C) is important in the normal processing of sensory information by the olfactory system. ..
  13. Mattei V, Barenco M, Tasciotti V, Garofalo T, Longo A, Boller K, et al. Paracrine diffusion of PrP(C) and propagation of prion infectivity by plasma membrane-derived microvesicles. PLoS ONE. 2009;4:e5057 pubmed publisher
    ..The data suggest that MVs may contribute both to the intercellular mechanism(s) of PrP(C) diffusion and signaling as well as to the process of prion spread and neuroinvasion. ..
  14. Caputo A, Sarnataro D, Campana V, Costanzo M, Negro A, Sorgato M, et al. Doppel and PrPC co-immunoprecipitate in detergent-resistant membrane domains of epithelial FRT cells. Biochem J. 2009;425:341-51 pubmed publisher
    ..Furthermore, both Dpl and PrPC could be immunoprecipitated with flotillin-2, a raft protein involved in endocytosis and cell signalling events, suggesting that they share the same lipid environment. ..
  15. Kessels H, Nguyen L, Nabavi S, Malinow R. The prion protein as a receptor for amyloid-beta. Nature. 2010;466:E3-4; discussion E4-5 pubmed publisher
    ..Here we show that PrP(C) is not required for amyloid-beta-induced synaptic depression, reduction in spine density, or blockade of LTP; our results indicate that amyloid-beta-mediated synaptic defects do not require PrP(c)...
  16. Karapetyan Y, Saa P, Mahal S, Sferrazza G, Sherman A, Sales N, et al. Prion strain discrimination based on rapid in vivo amplification and analysis by the cell panel assay. PLoS ONE. 2009;4:e5730 pubmed publisher
    ..We show that in these mice the four prion strains examined are rapidly and faithfully amplified and can subsequently be discriminated by a cell-based procedure, the Cell Panel Assay. ..
  17. Gambetti P, Cali I, Notari S, Kong Q, Zou W, Surewicz W. Molecular biology and pathology of prion strains in sporadic human prion diseases. Acta Neuropathol. 2011;121:79-90 pubmed publisher
    ..However, the intrinsic characteristics that distinguish at least four of these strains remain to be identified. ..
  18. Chen S, Yadav S, Surewicz W. Interaction between human prion protein and amyloid-beta (Abeta) oligomers: role OF N-terminal residues. J Biol Chem. 2010;285:26377-83 pubmed publisher
    ..This insight may help explain the interplay between the postulated protective and pathogenic roles of PrP in AD and may contribute to the development of novel therapeutic strategies as well. ..
  19. Nicolas O, Gavin R, Del Río J. New insights into cellular prion protein (PrPc) functions: the "ying and yang" of a relevant protein. Brain Res Rev. 2009;61:170-84 pubmed publisher
    ..In this review, we summarize new findings on PrP(c) functions, especially those related to neural degeneration and cell signaling. ..
  20. Taylor D, Parkin E, Cocklin S, Ault J, Ashcroft A, Turner A, et al. Role of ADAMs in the ectodomain shedding and conformational conversion of the prion protein. J Biol Chem. 2009;284:22590-600 pubmed publisher
    ..Collectively, these data indicate that although PrP(C) can be shed through the action of ADAM family members, modulation of PrP(C) or PrP(Sc) ectodomain shedding does not regulate prion conversion. ..
  21. Hachiya N, Komata Y, Harguem S, Nishijima K, Kaneko K. Possible involvement of calpain-like activity in normal processing of cellular prion protein. Neurosci Lett. 2011;490:150-5 pubmed publisher
    ..These results suggest that a calpain-like activity mediates normal processing of PrP(C) in N2a cells. ..
  22. Pradines E, Loubet D, Schneider B, Launay J, Kellermann O, Mouillet Richard S. CREB-dependent gene regulation by prion protein: impact on MMP-9 and beta-dystroglycan. Cell Signal. 2008;20:2050-8 pubmed publisher
    ..Taken together, our data define molecular mechanisms that likely mirror PrP(C) ubiquitous contribution to cytoprotection and its involvement in neuronal plasticity. ..
  23. Ostapchenko V, Makarava N, Savtchenko R, Baskakov I. The polybasic N-terminal region of the prion protein controls the physical properties of both the cellular and fibrillar forms of PrP. J Mol Biol. 2008;383:1210-24 pubmed publisher
    ..This work also suggests that this region could regulate diversity of prion strains or subtypes despite its remote location from the prion folding domain. ..
  24. Ingram R, Isaacs J, Kaur G, Lowther D, Reynolds C, Boyton R, et al. A role of cellular prion protein in programming T-cell cytokine responses in disease. FASEB J. 2009;23:1672-84 pubmed publisher
    ..The findings indicate that PrP(C) is a potentially important molecule influencing T-cell activation and effector function. ..
  25. Murakami K, Nishikawa F, Noda K, Yokoyama T, Nishikawa S. Anti-bovine prion protein RNA aptamer containing tandem GGA repeat interacts both with recombinant bovine prion protein and its beta isoform with high affinity. Prion. 2008;2:73-80 pubmed
    ..This minimized form of aptamer #1 may therefore be useful in the detection of bPrP, diagnosis of prion disease, enrichment of bPr and ultimately in gaining a better understanding of prion diseases. ..
  26. Morel E, Fouquet S, Strup Perrot C, Pichol Thievend C, Thievend C, Petit C, et al. The cellular prion protein PrP(c) is involved in the proliferation of epithelial cells and in the distribution of junction-associated proteins. PLoS ONE. 2008;3:e3000 pubmed publisher
    ..From these results, PrP(c) could be considered as a new partner involved in the balance between proliferation and polarization/differentiation in epithelial cells. ..
  27. Gimbel D, Nygaard H, Coffey E, Gunther E, Lauren J, Gimbel Z, et al. Memory impairment in transgenic Alzheimer mice requires cellular prion protein. J Neurosci. 2010;30:6367-74 pubmed publisher
    ..Thus, deletion of PrP(C) expression dissociates Abeta accumulation from behavioral impairment in these AD mice, with the cognitive deficits selectively requiring PrP(C). ..
  28. Lee Y, Baskakov I. Treatment with normal prion protein delays differentiation and helps to maintain high proliferation activity in human embryonic stem cells. J Neurochem. 2010;114:362-73 pubmed publisher
    ..e. executed by endogenous PrP(C). Together with previous observations, these work support the hypothesis that PrP(C) is involved in regulating self-renewal/differentiation status of stem cells including hESCs. ..
  29. Bribian A, Fontana X, Llorens F, Gavin R, Reina M, Garcia Verdugo J, et al. Role of the cellular prion protein in oligodendrocyte precursor cell proliferation and differentiation in the developing and adult mouse CNS. PLoS ONE. 2012;7:e33872 pubmed publisher
    ..In addition, numerous NG2-positive cells were observed in cortical regions of adult PrP(c) knockout mice, although no significant changes in myelination can be seen, probably due to the death of surplus cells. ..
  30. Stella R, Cifani P, Peggion C, Hansson K, Lazzari C, Bendz M, et al. Relative quantification of membrane proteins in wild-type and prion protein (PrP)-knockout cerebellar granule neurons. J Proteome Res. 2012;11:523-36 pubmed publisher
    ..The differentially expressed proteins identified using this approach were further analyzed by multiple reaction monitoring to confirm the expression level changes. ..
  31. Wolschner C, Giese A, Kretzschmar H, Huber R, Moroder L, Budisa N. Design of anti- and pro-aggregation variants to assess the effects of methionine oxidation in human prion protein. Proc Natl Acad Sci U S A. 2009;106:7756-61 pubmed publisher
    ..Accordingly, sporadic prion and other neurodegenerative diseases, as well as various aging processes, might also be caused by oxidative stress leading to Met oxidation...
  32. Sorgato M, Peggion C, Bertoli A. Is, indeed, the prion protein a Harlequin servant of "many" masters?. Prion. 2009;3:202-5 pubmed
  33. Guillot Sestier M, Sunyach C, Druon C, Scarzello S, Checler F. The alpha-secretase-derived N-terminal product of cellular prion, N1, displays neuroprotective function in vitro and in vivo. J Biol Chem. 2009;284:35973-86 pubmed publisher
    ..It further demonstrates that distinct N-terminal cleavage products of PrP(c) harbor different biological activities underlying the various phenotypes linking PrP(c) to cell survival. ..
  34. Wang F, Wang X, Ma J. Conversion of bacterially expressed recombinant prion protein. Methods. 2011;53:208-13 pubmed publisher
    ..The establishment of the in vitro recombinant PrP conversion assay makes it feasible for us to explore the molecular basis behind the intriguing properties associated with prion infectivity. ..
  35. Yang W, Cook J, Rassbach B, Lemus A, Dearmond S, Mastrianni J. A New Transgenic Mouse Model of Gerstmann-Straussler-Scheinker Syndrome Caused by the A117V Mutation of PRNP. J Neurosci. 2009;29:10072-80 pubmed publisher
    ..The occasional variation in histopathology they exhibit may shed light on a similar observation in human GSS(A117V). ..
  36. You H, Tsutsui S, Hameed S, Kannanayakal T, Chen L, Xia P, et al. A? neurotoxicity depends on interactions between copper ions, prion protein, and N-methyl-D-aspartate receptors. Proc Natl Acad Sci U S A. 2012;109:1737-42 pubmed publisher
  37. Turnbaugh J, Unterberger U, Saa P, Massignan T, Fluharty B, Bowman F, et al. The N-terminal, polybasic region of PrP(C) dictates the efficiency of prion propagation by binding to PrP(Sc). J Neurosci. 2012;32:8817-30 pubmed publisher
    ..It may be possible to specifically target this region for treatment of prion diseases as well as other neurodegenerative disorders due to ?-sheet-rich oligomers that bind to PrP(C). ..
  38. Um J, Kaufman A, Kostylev M, Heiss J, Stagi M, Takahashi H, et al. Metabotropic glutamate receptor 5 is a coreceptor for Alzheimer a? oligomer bound to cellular prion protein. Neuron. 2013;79:887-902 pubmed publisher
    ..For mice expressing familial AD transgenes, mGluR5 antagonism reverses deficits in learning, memory, and synapse density. Thus, A?o-PrP(C) complexes at the neuronal surface activate mGluR5 to disrupt neuronal function. ..
  39. Canello T, Frid K, Gabizon R, Lisa S, Friedler A, Moskovitz J, et al. Oxidation of Helix-3 methionines precedes the formation of PK resistant PrP. PLoS Pathog. 2010;6:e1000977 pubmed publisher
  40. Löfgren K, Cheng F, Fransson L, Bedecs K, Mani K. Involvement of glypican-1 autoprocessing in scrapie infection. Eur J Neurosci. 2008;28:964-72 pubmed publisher
    ..These results suggest a role for Gpc-1 autoprocessing in the clearance of PrP(Sc) from infected cells. ..
  41. Silva C, Onisko B, Dynin I, Erickson M, Vensel W, Requena J, et al. Assessing the role of oxidized methionine at position 213 in the formation of prions in hamsters. Biochemistry. 2010;49:1854-61 pubmed publisher
    ..These strains show only low levels of MetSO213 that is comparable to that of PrP(C). These data suggest that MetSO213 does not appear to be a prion-specific covalent signature. ..
  42. Godsave S, Wille H, Kujala P, Latawiec D, Dearmond S, Serban A, et al. Cryo-immunogold electron microscopy for prions: toward identification of a conversion site. J Neurosci. 2008;28:12489-99 pubmed publisher
    ..Trypsin digestion of infected hippocampal sections resulted in a reduction in R2 labeling of >85%, which suggests that a high proportion of PrP(Sc) may be oligomeric, protease-sensitive PrP(Sc). ..
  43. Pantera B, Bini C, Cirri P, Paoli P, Camici G, Manao G, et al. PrPc activation induces neurite outgrowth and differentiation in PC12 cells: role for caveolin-1 in the signal transduction pathway. J Neurochem. 2009;110:194-207 pubmed publisher
    ..Furthermore our data support a significant role for PrP(c) as a response mediator in neuritogenesis and cell differentiation. ..
  44. Gossner A, Bennet N, Hunter N, Hopkins J. Differential expression of Prnp and Sprn in scrapie infected sheep also reveals Prnp genotype specific differences. Biochem Biophys Res Commun. 2009;378:862-6 pubmed publisher
    ..In addition, infection with SSBP/1 scrapie seems to have little effect on either PrP or Shadoo expression levels. ..
  45. Abalos G, Cruite J, Bellon A, Hemmers S, Akagi J, Mastrianni J, et al. Identifying key components of the PrPC-PrPSc replicative interface. J Biol Chem. 2008;283:34021-8 pubmed publisher
  46. Hosszu L, Trevitt C, Jones S, Batchelor M, Scott D, Jackson G, et al. Conformational properties of beta-PrP. J Biol Chem. 2009;284:21981-90 pubmed publisher
    ..This precursor state is almost as compact as the folded PrPC structure and, as it assembles, only residues 126-227 are immobilized within the oligomeric structure, leaving the remainder in a mobile, random-coil state. ..
  47. Henriques S, Pattenden L, Aguilar M, Castanho M. The toxicity of prion protein fragment PrP(106-126) is not mediated by membrane permeabilization as shown by a M112W substitution. Biochemistry. 2009;48:4198-208 pubmed publisher
    ..These results further support the idea that PrP(106-126) toxicity is not a consequence of peptide-membrane interaction and pore formation. ..
  48. Schneider B, Pietri M, Pradines E, Loubet D, Launay J, Kellermann O, et al. Understanding the neurospecificity of Prion protein signaling. Front Biosci (Landmark Ed). 2011;16:169-86 pubmed
  49. Rial D, Duarte F, Xikota J, Schmitz A, Dafré A, Figueiredo C, et al. Cellular prion protein modulates age-related behavioral and neurochemical alterations in mice. Neuroscience. 2009;164:896-907 pubmed publisher
  50. Westaway D, Genovesi S, Daude N, Brown R, Lau A, Lee I, et al. Down-regulation of Shadoo in prion infections traces a pre-clinical event inversely related to PrP(Sc) accumulation. PLoS Pathog. 2011;7:e1002391 pubmed publisher
    ..This cellular response may offer new insights into the homeostatic mechanisms involved in detection and clearance of the misfolded proteins that drive prion disease pathogenesis. ..
  51. Choi Y, Gröner A, Ironside J, Head M. Correlation of polydispersed prion protein and characteristic pathology in the thalamus in variant Creutzfeldt-Jakob disease: implication of small oligomeric species. Brain Pathol. 2011;21:298-307 pubmed publisher
  52. Anantharam V, Kanthasamy A, Choi C, Martin D, Latchoumycandane C, Richt J, et al. Opposing roles of prion protein in oxidative stress- and ER stress-induced apoptotic signaling. Free Radic Biol Med. 2008;45:1530-41 pubmed publisher
  53. Stöhr J, Watts J, Legname G, Oehler A, Lemus A, Nguyen H, et al. Spontaneous generation of anchorless prions in transgenic mice. Proc Natl Acad Sci U S A. 2011;108:21223-8 pubmed publisher
    ..Remarkably, disease from ill Tg(PrP,?GPI) mice transmitted to mice expressing wild-type PrP(C), indicating the spontaneous generation of prions. ..
  54. Miller M, Geoghegan J, Supattapone S. Dissociation of infectivity from seeding ability in prions with alternate docking mechanism. PLoS Pathog. 2011;7:e1002128 pubmed publisher
    ..These results suggest that the propagation of PrP(Sc) molecules may not depend on a single stereotypic mechanism, but that normal PrP(C)/PrP(Sc) interaction through polybasic domains may be required to generate prion infectivity. ..
  55. Hara H, Okemoto Nakamura Y, Shinkai Ouchi F, Hanada K, Yamakawa Y, Hagiwara K. Mouse prion protein (PrP) segment 100 to 104 regulates conversion of PrP(C) to PrP(Sc) in prion-infected neuroblastoma cells. J Virol. 2012;86:5626-36 pubmed publisher
    ..These results suggest the segment 100 to 104 of MoPrP(C) plays a key role in conversion after binding to MoPrP(Sc). ..
  56. Walmsley A, Watt N, Taylor D, Perera W, Hooper N. alpha-cleavage of the prion protein occurs in a late compartment of the secretory pathway and is independent of lipid rafts. Mol Cell Neurosci. 2009;40:242-8 pubmed publisher
    ..Our data thus demonstrate that the alpha-cleavage of PrP(C) occurs predominantly in a raft-independent manner in a late compartment of the secretory pathway. ..
  57. Yam A, Gao C, Wang X, Wu P, Peretz D. The octarepeat region of the prion protein is conformationally altered in PrP(Sc). PLoS ONE. 2010;5:e9316 pubmed publisher
    ..This phenomenon may be relevant to the mechanism by which the amino terminus of PrP(C) participates in PrP(Sc) conversion, and may also be exploited for diagnostic purposes. ..
  58. Minaki H, Sasaki K, Honda H, Iwaki T. Prion protein oligomers in Creutzfeldt-Jakob disease detected by gel-filtration centrifuge columns. Neuropathology. 2009;29:536-42 pubmed publisher
    ..Dynamic changes of both oligomerization of the human PrP and depletion of normal PrP(c) require further elucidation to develop a greater understanding of the pathogenesis of human prion diseases. ..
  59. Sakthivelu V, Seidel R, Winklhofer K, Tatzelt J. Conserved stress-protective activity between prion protein and Shadoo. J Biol Chem. 2011;286:8901-8 pubmed publisher
    ..Our study reveals a conserved physiological activity between PrP(C) and Sho to protect cells from stress-induced toxicity and suggests that Sho and PrP(C) might act on similar signaling pathways. ..
  60. Angers R, Kang H, Napier D, Browning S, Seward T, Mathiason C, et al. Prion strain mutation determined by prion protein conformational compatibility and primary structure. Science. 2010;328:1154-8 pubmed publisher
    ..The primary structures of deer and elk prion proteins differ at residue 226, which, in concert with PrPSc conformational compatibility, determines prion strain mutation in these cervids. ..
  61. Taylor D, Whitehouse I, Hooper N. Glypican-1 mediates both prion protein lipid raft association and disease isoform formation. PLoS Pathog. 2009;5:e1000666 pubmed publisher
    ..These data indicate that glypican-1 is a novel cellular cofactor for prion conversion and we propose that it acts as a scaffold facilitating the interaction of PrP(C) and PrP(Sc) in lipid rafts. ..
  62. Massignan T, Stewart R, Biasini E, Solomon I, Bonetto V, Chiesa R, et al. A novel, drug-based, cellular assay for the activity of neurotoxic mutants of the prion protein. J Biol Chem. 2010;285:7752-65 pubmed publisher
    ..Our results establish a screenable cellular phenotype for the activity of neurotoxic forms of PrP, and they suggest possible mechanisms by which these molecules could produce their pathological effects in vivo. ..
  63. Moore S, Simmons M, Chaplin M, Spiropoulos J. Neuroanatomical distribution of abnormal prion protein in naturally occurring atypical scrapie cases in Great Britain. Acta Neuropathol. 2008;116:547-59 pubmed publisher
    ..It also reinforces the current recommendation to collect cerebellum in addition to brainstem to enable confident confirmation of this distinct disease phenotype within surveillance programmes...
  64. Tsutsui S, Hahn J, Johnson T, Ali Z, Jirik F. Absence of the cellular prion protein exacerbates and prolongs neuroinflammation in experimental autoimmune encephalomyelitis. Am J Pathol. 2008;173:1029-41 pubmed publisher
    ..Attenuation of T cell-dependent neuroinflammation thus represents a potential novel function of PrP C. ..
  65. Velayos J, Irujo A, Cuadrado Tejedor M, Paternain B, Moleres F, Ferrer V. The cellular prion protein and its role in Alzheimer disease. Prion. 2009;3:110-7 pubmed
    ..The work was done according to Helsinki Declaration of 1975, and approved by the Ethics Committee of the Faculty of Medicine of the University of Navarre. ..
  66. Puig B, Altmeppen H, Thurm D, Geissen M, Conrad C, Braulke T, et al. N-glycans and glycosylphosphatidylinositol-anchor act on polarized sorting of mouse PrP(C) in Madin-Darby canine kidney cells. PLoS ONE. 2011;6:e24624 pubmed publisher
    ..Exchange of the PrP(C) GPI-anchor for the one of Thy-1 redirects PrP(C) to the apical membrane. In conclusion, both N-glycosylation and GPI-anchor act on polarized sorting of PrP(C), with the GPI-anchor being dominant over N-glycans. ..
  67. Oliveira Martins J, Yusa S, Calella A, Bridel C, Baumann F, Dametto P, et al. Unexpected tolerance of alpha-cleavage of the prion protein to sequence variations. PLoS ONE. 2010;5:e9107 pubmed publisher
    ..These results suggest that alpha-cleavage is executed by an alpha-PrPase whose activity, despite surprisingly limited sequence specificity, is dependent on the size of the central region of PrP(C). ..
  68. Herva M, Relaño Ginés A, Villa A, Torres J. Prion infection of differentiated neurospheres. J Neurosci Methods. 2010;188:270-5 pubmed publisher
    ..These results suggest that differentiated neurosphere cultures can complement prion bioassays in mouse models. ..
  69. Sandberg M, Al Doujaily H, Sharps B, Clarke A, Collinge J. Prion propagation and toxicity in vivo occur in two distinct mechanistic phases. Nature. 2011;470:540-2 pubmed publisher
    ..Production of neurotoxic species is triggered when prion propagation saturates, leading to a switch from autocatalytic production of infectivity (phase 1) to a toxic (phase 2) pathway. ..
  70. Nieznanski K. Interactions of prion protein with intracellular proteins: so many partners and no consequences?. Cell Mol Neurobiol. 2010;30:653-66 pubmed publisher
    ..This review is focused on the cytoplasmic partners of PrP along with possible consequences of their binding. ..
  71. Chiesa R, Piccardo P, Biasini E, Ghetti B, Harris D. Aggregated, wild-type prion protein causes neurological dysfunction and synaptic abnormalities. J Neurosci. 2008;28:13258-67 pubmed publisher
  72. Hedlin P, Cashman N, Li L, Gupta J, Babiuk L, Potter A, et al. Design and delivery of a cryptic PrP(C) epitope for induction of PrP(Sc)-specific antibody responses. Vaccine. 2010;28:981-8 pubmed publisher
    ..Antigen specific antibodies are also present within cerebral spinal fluid and mucosal secretions. These characteristics provide a foundation for development of a TSE vaccine. ..
  73. Bremer J, Baumann F, Tiberi C, Wessig C, Fischer H, Schwarz P, et al. Axonal prion protein is required for peripheral myelin maintenance. Nat Neurosci. 2010;13:310-8 pubmed publisher
    ..These results indicate that neuronal expression and regulated proteolysis of PrP(C) are essential for myelin maintenance. ..
  74. Kudo W, Lee H, Zou W, Wang X, Perry G, Zhu X, et al. Cellular prion protein is essential for oligomeric amyloid-?-induced neuronal cell death. Hum Mol Genet. 2012;21:1138-44 pubmed publisher
    ..These findings are the first to demonstrate that PrP(C) is required for A? oligomer-induced neuronal cell death, the pathology essential to cognitive loss. ..
  75. Colombo G, Meli M, Morra G, Gabizon R, Gasset M. Methionine sulfoxides on prion protein Helix-3 switch on the alpha-fold destabilization required for conversion. PLoS ONE. 2009;4:e4296 pubmed publisher
    ..Our results suggest that the sulfoxidation of Helix-3 methionines might be the switch for triggering the initial alpha-fold destabilization required for the productive pathogenic conversion. ..
  76. Westergard L, Turnbaugh J, Harris D. A nine amino acid domain is essential for mutant prion protein toxicity. J Neurosci. 2011;31:14005-17 pubmed publisher
    ..This finding identifies a protein domain that may serve as a drug target for amelioration of prion neurotoxicity. ..
  77. Barry A, Klyubin I, Mc Donald J, Mably A, Farrell M, Scott M, et al. Alzheimer's disease brain-derived amyloid-?-mediated inhibition of LTP in vivo is prevented by immunotargeting cellular prion protein. J Neurosci. 2011;31:7259-63 pubmed publisher
    ..These data support the pathophysiological significance of SDS-stable A? dimer and the role of PrP(C) in mediating synaptic plasticity disruption by soluble A?. ..
  78. Caetano F, Beraldo F, Hajj G, Guimaraes A, Jürgensen S, Wasilewska Sampaio A, et al. Amyloid-beta oligomers increase the localization of prion protein at the cell surface. J Neurochem. 2011;117:538-53 pubmed publisher
    ..Our experiments show for the first time that A? oligomers signal in a PrP(C)-dependent way and that they can affect PrP(C) trafficking, increasing its localization at the cell surface. ..