Prnp

Summary

Gene Symbol: Prnp
Description: prion protein
Alias: AA960666, AI325101, CD230, PrP, PrP, PrPC, PrPSc, Prn-i, Prn-p, Sinc, prP27-30, prP33-35C, major prion protein
Species: mouse
Products:     Prnp

Top Publications

  1. Shi F, Yang L, Kouadir M, Yang Y, Ding T, Wang J, et al. Prion protein participates in the regulation of classical and alternative activation of BV2 microglia. J Neurochem. 2013;124:168-74 pubmed publisher
    ..We first examined the mRNA expression of PRNP upon exposure to IFN-?, IL-4, or IL-10 in BV2 microglia...
  2. Kim J, Surewicz K, Gambetti P, Surewicz W. The role of glycophosphatidylinositol anchor in the amplification of the scrapie isoform of prion protein in vitro. FEBS Lett. 2009;583:3671-5 pubmed publisher
    Transmissible spongiform encephalopathies are associated with an autocatalytic conversion of normal prion protein, PrP(C), to a protease-resistant form, PrPres...
  3. Martin S, Burón I, Espinosa J, Castilla J, Villalba J, Torres J. Coenzyme Q and protein/lipid oxidation in a BSE-infected transgenic mouse model. Free Radic Biol Med. 2007;42:1723-9 pubmed
    ..intracerebral bovine spongiform encephalopathy (BSE) infection of transgenic mice expressing bovine prion protein (PrP)...
  4. Encalada S, Szpankowski L, Xia C, Goldstein L. Stable kinesin and dynein assemblies drive the axonal transport of mammalian prion protein vesicles. Cell. 2011;144:551-65 pubmed publisher
    ..we characterize the intracellular transport and steady-state motor subunit composition of mammalian prion protein (PrP(C)) vesicles...
  5. Nunziante M, Ackermann K, Dietrich K, Wolf H, Gädtke L, Gilch S, et al. Proteasomal dysfunction and endoplasmic reticulum stress enhance trafficking of prion protein aggregates through the secretory pathway and increase accumulation of pathologic prion protein. J Biol Chem. 2011;286:33942-53 pubmed publisher
    A conformational change of the cellular prion protein (PrP(c)) underlies formation of PrP(Sc), which is closely associated with pathogenesis and transmission of prion diseases...
  6. Jackson W, Borkowski A, Faas H, Steele A, King O, Watson N, et al. Spontaneous generation of prion infectivity in fatal familial insomnia knockin mice. Neuron. 2009;63:438-50 pubmed publisher
    A crucial tenet of the prion hypothesis is that misfolding of the prion protein (PrP) induced by mutations associated with familial prion disease is, in an otherwise normal mammalian brain, sufficient to generate the infectious agent...
  7. Bradford B, Tuzi N, Feltri M, McCorquodale C, Cancellotti E, Manson J. Dramatic reduction of PrP C level and glycosylation in peripheral nerves following PrP knock-out from Schwann cells does not prevent transmissible spongiform encephalopathy neuroinvasion. J Neurosci. 2009;29:15445-54 pubmed publisher
    Expression of the prion protein (PrP(C)) is a requirement for host susceptibility to the transmissible spongiform encephalopathies (TSEs) and thought to be necessary for the replication and transport of the infectious agent...
  8. Lobão Soares B, Walz R, Carlotti C, Sakamoto A, Calvo F, Terzian A, et al. Cellular prion protein regulates the motor behaviour performance and anxiety-induced responses in genetically modified mice. Behav Brain Res. 2007;183:87-94 pubmed
    ..test) in Zurich developed wild-type adult mice (WT, controls of normal PrP(C) expression), in knockout (KO) mice (Prnp(0/0), with no PrP(C) expression), and in PrP(C) overexpressing Tg-20 mice...
  9. Biasini E, Tapella L, Restelli E, Pozzoli M, Massignan T, Chiesa R. The hydrophobic core region governs mutant prion protein aggregation and intracellular retention. Biochem J. 2010;430:477-86 pubmed publisher
    ..prion diseases have a pattern of autosomal dominant inheritance, and are linked to mutations in the gene encoding PrP (prion protein), a GPI (glycosylphosphatidylinositol)-anchored protein whose function is not clear...
  10. Nicolas O, Gavin R, Braun N, Ureña J, Fontana X, Soriano E, et al. Bcl-2 overexpression delays caspase-3 activation and rescues cerebellar degeneration in prion-deficient mice that overexpress amino-terminally truncated prion. FASEB J. 2007;21:3107-17 pubmed
    Prnp knockout mice that overexpress an amino-truncated form of PrPc (deltaPrP) are ataxic and display cerebellar cell loss and premature death...

Detail Information

Publications95

  1. Shi F, Yang L, Kouadir M, Yang Y, Ding T, Wang J, et al. Prion protein participates in the regulation of classical and alternative activation of BV2 microglia. J Neurochem. 2013;124:168-74 pubmed publisher
    ..We first examined the mRNA expression of PRNP upon exposure to IFN-?, IL-4, or IL-10 in BV2 microglia...
  2. Kim J, Surewicz K, Gambetti P, Surewicz W. The role of glycophosphatidylinositol anchor in the amplification of the scrapie isoform of prion protein in vitro. FEBS Lett. 2009;583:3671-5 pubmed publisher
    Transmissible spongiform encephalopathies are associated with an autocatalytic conversion of normal prion protein, PrP(C), to a protease-resistant form, PrPres...
  3. Martin S, Burón I, Espinosa J, Castilla J, Villalba J, Torres J. Coenzyme Q and protein/lipid oxidation in a BSE-infected transgenic mouse model. Free Radic Biol Med. 2007;42:1723-9 pubmed
    ..intracerebral bovine spongiform encephalopathy (BSE) infection of transgenic mice expressing bovine prion protein (PrP)...
  4. Encalada S, Szpankowski L, Xia C, Goldstein L. Stable kinesin and dynein assemblies drive the axonal transport of mammalian prion protein vesicles. Cell. 2011;144:551-65 pubmed publisher
    ..we characterize the intracellular transport and steady-state motor subunit composition of mammalian prion protein (PrP(C)) vesicles...
  5. Nunziante M, Ackermann K, Dietrich K, Wolf H, Gädtke L, Gilch S, et al. Proteasomal dysfunction and endoplasmic reticulum stress enhance trafficking of prion protein aggregates through the secretory pathway and increase accumulation of pathologic prion protein. J Biol Chem. 2011;286:33942-53 pubmed publisher
    A conformational change of the cellular prion protein (PrP(c)) underlies formation of PrP(Sc), which is closely associated with pathogenesis and transmission of prion diseases...
  6. Jackson W, Borkowski A, Faas H, Steele A, King O, Watson N, et al. Spontaneous generation of prion infectivity in fatal familial insomnia knockin mice. Neuron. 2009;63:438-50 pubmed publisher
    A crucial tenet of the prion hypothesis is that misfolding of the prion protein (PrP) induced by mutations associated with familial prion disease is, in an otherwise normal mammalian brain, sufficient to generate the infectious agent...
  7. Bradford B, Tuzi N, Feltri M, McCorquodale C, Cancellotti E, Manson J. Dramatic reduction of PrP C level and glycosylation in peripheral nerves following PrP knock-out from Schwann cells does not prevent transmissible spongiform encephalopathy neuroinvasion. J Neurosci. 2009;29:15445-54 pubmed publisher
    Expression of the prion protein (PrP(C)) is a requirement for host susceptibility to the transmissible spongiform encephalopathies (TSEs) and thought to be necessary for the replication and transport of the infectious agent...
  8. Lobão Soares B, Walz R, Carlotti C, Sakamoto A, Calvo F, Terzian A, et al. Cellular prion protein regulates the motor behaviour performance and anxiety-induced responses in genetically modified mice. Behav Brain Res. 2007;183:87-94 pubmed
    ..test) in Zurich developed wild-type adult mice (WT, controls of normal PrP(C) expression), in knockout (KO) mice (Prnp(0/0), with no PrP(C) expression), and in PrP(C) overexpressing Tg-20 mice...
  9. Biasini E, Tapella L, Restelli E, Pozzoli M, Massignan T, Chiesa R. The hydrophobic core region governs mutant prion protein aggregation and intracellular retention. Biochem J. 2010;430:477-86 pubmed publisher
    ..prion diseases have a pattern of autosomal dominant inheritance, and are linked to mutations in the gene encoding PrP (prion protein), a GPI (glycosylphosphatidylinositol)-anchored protein whose function is not clear...
  10. Nicolas O, Gavin R, Braun N, Ureña J, Fontana X, Soriano E, et al. Bcl-2 overexpression delays caspase-3 activation and rescues cerebellar degeneration in prion-deficient mice that overexpress amino-terminally truncated prion. FASEB J. 2007;21:3107-17 pubmed
    Prnp knockout mice that overexpress an amino-truncated form of PrPc (deltaPrP) are ataxic and display cerebellar cell loss and premature death...
  11. Chadi S, Young R, Le Guillou S, Tilly G, Bitton F, Martin Magniette M, et al. Brain transcriptional stability upon prion protein-encoding gene invalidation in zygotic or adult mouse. BMC Genomics. 2010;11:448 pubmed publisher
    ..Only subtle transcriptomic differences resulting from the Prnp knockout could be evidenced, beside Prnp itself, in the analyzed adult brains following microarray analysis of 24 ..
  12. 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
    The cellular form of the prion protein, PrP(C), undergoes extensive proteolysis at the alpha site (109K [see text]H110)...
  13. Cisse M, Sanchez P, Kim D, Ho K, Yu G, Mucke L. Ablation of cellular prion protein does not ameliorate abnormal neural network activity or cognitive dysfunction in the J20 line of human amyloid precursor protein transgenic mice. J Neurosci. 2011;31:10427-31 pubmed publisher
    Previous studies suggested that the cellular prion protein (PrP(c)) plays a critical role in the pathogenesis of Alzheimer's disease (AD)...
  14. Benvegnù S, Poggiolini I, Legname G. Neurodevelopmental expression and localization of the cellular prion protein in the central nervous system of the mouse. J Comp Neurol. 2010;518:1879-91 pubmed publisher
    Transmissible spongiform encephalopathies (TSEs) are neurodegenerative disorders caused by PrP(Sc), or prion, an abnormally folded form of the cellular prion protein (PrP(C))...
  15. 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
    ..Here we found a previously unknown behavioral phenotype of Prnp(-/-) mice in an odor-guided task...
  16. Parkin E, Watt N, Hussain I, Eckman E, Eckman C, Manson J, et al. Cellular prion protein regulates beta-secretase cleavage of the Alzheimer's amyloid precursor protein. Proc Natl Acad Sci U S A. 2007;104:11062-7 pubmed
    ..The normal cellular function of the prion protein (PrP(C)), the causative agent of the transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease in ..
  17. Deleault N, Walsh D, Piro J, Wang F, Wang X, Ma J, et al. Cofactor molecules maintain infectious conformation and restrict strain properties in purified prions. Proc Natl Acad Sci U S A. 2012;109:E1938-46 pubmed publisher
    Prions containing misfolded prion protein (PrP(Sc)) can be formed with cofactor molecules using the technique of serial protein misfolding cyclic amplification...
  18. 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
    ..precursor cell (OPC) proliferation and differentiation, although the contribution of the cellular prion protein (PrP(c)) to this process remains unclear...
  19. 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
    ..Here we show that ablation of the prion protein PrP(C) triggers a chronic demyelinating polyneuropathy (CDP) in four independently targeted mouse strains...
  20. Solomon I, Khatri N, Biasini E, Massignan T, Huettner J, Harris D. An N-terminal polybasic domain and cell surface localization are required for mutant prion protein toxicity. J Biol Chem. 2011;286:14724-36 pubmed publisher
    There is evidence that alterations in the normal physiological activity of PrP(C) contribute to prion-induced neurotoxicity...
  21. Mays C, Titlow W, Seward T, Telling G, Ryou C. Enhancement of protein misfolding cyclic amplification by using concentrated cellular prion protein source. Biochem Biophys Res Commun. 2009;388:306-10 pubmed publisher
    ..However, constraints affecting PMCA have not been well-defined. Although cellular prion protein (PrP(C)) is required for prion replication, the influence of PrP(C) abundance on PMCA has not been assessed...
  22. McCulloch L, Brown K, Bradford B, Hopkins J, Bailey M, Rajewsky K, et al. Follicular dendritic cell-specific prion protein (PrP) expression alone is sufficient to sustain prion infection in the spleen. PLoS Pathog. 2011;7:e1002402 pubmed publisher
    ..In the attempts to-date to establish the role of FDC in prion pathogenesis it was not possible to dissociate the Prnp expression of FDC from that of the nervous system and all other non-haematopoietic lineages...
  23. 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
    In prion disease, direct interaction between the cellular prion protein (PrP(C)) and its misfolded disease-associated conformer PrP(Sc) is a crucial, although poorly understood step promoting the formation of nascent PrP(Sc) and prion ..
  24. Hajj G, Lopes M, Mercadante A, Veiga S, da Silveira R, Santos T, et al. Cellular prion protein interaction with vitronectin supports axonal growth and is compensated by integrins. J Cell Sci. 2007;120:1915-26 pubmed
    The physiological functions of the cellular prion protein, PrP(C), as a cell surface pleiotropic receptor are under debate. We report that PrP(C) interacts with vitronectin but not with fibronectin or collagen...
  25. 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
    Endoproteolysis of the cellular prion protein (PrP(C)) modulates both the normal function of the protein and the pathogenesis of the neurodegenerative prion diseases...
  26. Smirnovas V, Baron G, Offerdahl D, Raymond G, Caughey B, Surewicz W. Structural organization of brain-derived mammalian prions examined by hydrogen-deuterium exchange. Nat Struct Mol Biol. 2011;18:504-6 pubmed publisher
    One of the mysteries in prion research is the structure of the infectious form of mammalian prion protein PrP(Sc). Here we used mass spectrometry analysis of hydrogen-deuterium exchange to examine brain-derived PrP(Sc)...
  27. Chang J, Yang L, Kouadir M, Peng Y, Zhang S, Shi F, et al. Antibody-mediated inhibition of integrin ?5?1 blocks neurotoxic prion peptide PrP106-126-induced activation of BV2 microglia. J Mol Neurosci. 2012;48:248-52 pubmed publisher
    ..The identification of cell surface molecules that mediate the prion protein (PrP) synthetic peptide interaction with microglia is of great significance as it represents potential target molecules ..
  28. Haigh C, McGlade A, Lewis V, Masters C, Lawson V, Collins S. Acute exposure to prion infection induces transient oxidative stress progressing to be cumulatively deleterious with chronic propagation in vitro. Free Radic Biol Med. 2011;51:594-608 pubmed publisher
    ..Using cell culture models of prion infection we found that cells demonstrate a rapid, prion protein (PrP) dependent, increase in intracellular ROS following exposure to infectious inoculum...
  29. 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
    The neurotoxic forms of the prion protein (PrP) that cause neurodegeneration in prion diseases remain to be conclusively identified...
  30. Jen A, Parkyn C, Mootoosamy R, Ford M, Warley A, Liu Q, et al. Neuronal low-density lipoprotein receptor-related protein 1 binds and endocytoses prion fibrils via receptor cluster 4. J Cell Sci. 2010;123:246-55 pubmed publisher
    For infectious prion protein (designated PrP(Sc)) to act as a template to convert normal cellular protein (PrP(C)) to its distinctive pathogenic conformation, the two forms of prion protein (PrP) must interact closely...
  31. Strom A, Wang G, Scott F. Impaired glucose tolerance in mice lacking cellular prion protein. Pancreas. 2011;40:229-32 pubmed
    We previously demonstrated that the expression of cellular prion protein (PrPC) in islet [beta]-cells is suppressed in hyperglycemic rats suggesting a major role for PrPC in blood glucose regulation...
  32. Korom M, Wylie K, Wang H, Davis K, Sangabathula M, Delassus G, et al. A proautophagic antiviral role for the cellular prion protein identified by infection with a herpes simplex virus 1 ICP34.5 mutant. J Virol. 2013;87:5882-94 pubmed publisher
    The cellular prion protein (PrP) often plays a cytoprotective role by regulating autophagy in response to cell stress...
  33. Li A, Christensen H, Stewart L, Roth K, Chiesa R, Harris D. Neonatal lethality in transgenic mice expressing prion protein with a deletion of residues 105-125. EMBO J. 2007;26:548-58 pubmed
    To identify sequence domains important for the neurotoxic and neuroprotective activities of the prion protein (PrP), we have engineered transgenic mice that express a form of murine PrP deleted for a conserved block of 21 amino acids (..
  34. Polano M, Bek A, Benetti F, Lazzarino M, Legname G. Structural insights into alternate aggregated prion protein forms. J Mol Biol. 2009;393:1033-42 pubmed publisher
    The conversion of the cellular form of the prion protein (PrP(C)) to an abnormal, alternatively folded isoform (PrP(Sc)) is the central event in prion diseases or transmissible spongiform encephalopathies...
  35. Thaa B, Zahn R, Matthey U, Kroneck P, Burkle A, Fritz G. The deletion of amino acids 114-121 in the TM1 domain of mouse prion protein stabilizes its conformation but does not affect the overall structure. Biochim Biophys Acta. 2008;1783:1076-84 pubmed
    ..PrPDelta114-121) has previously been described to lack convertibility into the scrapie-associated isoform of PrP (PrPSc) and to exhibit a dominant-negative effect on the conversion of wild-type PrPC into PrPSc in living cells...
  36. Chiang Y, Otoshima Y, Watanabe Y, Inanami O, Shimoyama Y. Dynamics and local ordering of spin-labeled prion protein: an ESR simulation study of a highly PH-sensitive site. J Biomol Struct Dyn. 2008;26:355-66 pubmed
    ..It suggests a more mobile and disordered dynamic molecular structure for mouse PrPC, which is very likely correlated with increased beta-sheet content at low pH, as the environment changes from ..
  37. Baumann F, Tolnay M, Brabeck C, Pahnke J, Kloz U, Niemann H, et al. Lethal recessive myelin toxicity of prion protein lacking its central domain. EMBO J. 2007;26:538-47 pubmed
    b>PrP(C)-deficient mice expressing prion protein variants with large amino-proximal deletions (termed PrP(DeltaF)) suffer from neurodegeneration, which is rescued by full-length PrP(C)...
  38. Rushworth J, Griffiths H, Watt N, Hooper N. Prion protein-mediated toxicity of amyloid-? oligomers requires lipid rafts and the transmembrane LRP1. J Biol Chem. 2013;288:8935-51 pubmed publisher
    ..The cellular prion protein (PrP(C)) was recently identified as a high affinity neuronal receptor for A? oligomers...
  39. Zabel M, Heikenwalder M, Prinz M, Arrighi I, Schwarz P, Kranich J, et al. Stromal complement receptor CD21/35 facilitates lymphoid prion colonization and pathogenesis. J Immunol. 2007;179:6144-52 pubmed
    ..Further adoptive transfer experiments between WT mice and mice devoid of both the cellular prion protein PrP(C) and CD21/35 showed that splenic retention of inoculum depended on stromal CD21/35 expression...
  40. Priola S, McNally K. The role of the prion protein membrane anchor in prion infection. Prion. 2009;3:134-8 pubmed
    Normal cellular and abnormal disease-associated forms of prion protein (PrP) contain a C-terminal glycophosphatidyl-inositol (GPI) membrane anchor...
  41. Griffiths H, Whitehouse I, Baybutt H, Brown D, Kellett K, Jackson C, et al. Prion protein interacts with BACE1 protein and differentially regulates its activity toward wild type and Swedish mutant amyloid precursor protein. J Biol Chem. 2011;286:33489-500 pubmed publisher
    ..We have reported previously that the cellular prion protein (PrP(C)) inhibited the action of BACE1 toward human wild type APP (APP(WT)) in cellular models and that the levels of ..
  42. 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
    Prion propagation involves a templating reaction in which the infectious form of the prion protein (PrP(Sc)) binds to the cellular form (PrP(C)), generating additional molecules of PrP(Sc)...
  43. Prestori F, Rossi P, Bearzatto B, Laine J, Necchi D, Diwakar S, et al. Altered neuron excitability and synaptic plasticity in the cerebellar granular layer of juvenile prion protein knock-out mice with impaired motor control. J Neurosci. 2008;28:7091-103 pubmed publisher
    Although the role of abnormal prion protein (PrP) conformation in generating infectious brain diseases (transmissible spongiform encephalopathy) has been recognized, the function of PrP in the normal brain remains mostly unknown...
  44. 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
    Although the physiological roles of the cellular prion protein (PrP C) remain to be fully elucidated, PrP C has been proposed to represent a potential regulator of cellular immunity...
  45. Wegmann S, Miesbauer M, Winklhofer K, Tatzelt J, Muller D. Observing fibrillar assemblies on scrapie-infected cells. Pflugers Arch. 2008;456:83-93 pubmed publisher
    ..This scrapie-related prion protein (PrPSc) has an increased beta-sheet content, is detergent insoluble and proteinase K resistant, and accumulates in prion-..
  46. Hidaka K, Shirai M, Lee J, Wakayama T, Kodama I, Schneider M, et al. The cellular prion protein identifies bipotential cardiomyogenic progenitors. Circ Res. 2010;106:111-9 pubmed publisher
    ..Here, we show that cellular prion protein (PrP) serves as an effective surface marker for isolating nascent cardiomyocytes as well as cardiomyogenic progenitors...
  47. Caetano F, Lopes M, Hajj G, Machado C, Pinto Arantes C, Magalhaes A, et al. Endocytosis of prion protein is required for ERK1/2 signaling induced by stress-inducible protein 1. J Neurosci. 2008;28:6691-702 pubmed publisher
    ..STI1 triggers activation of protein kinase A (PKA) and ERK1/2 signaling by interacting with the cellular prion (PrP(C)) at the cell surface, resulting in neuroprotection and increased neuritogenesis...
  48. Uraki R, Sakudo A, Ando S, Kitani H, Onodera T. Enhancement of phagocytotic activity by prion protein in PrP-deficient macrophage cells. Int J Mol Med. 2010;26:527-32 pubmed
    ..cells, contribute to the pathogenesis of prion diseases by accumulating an abnormal isoform of prion protein (PrPSc), which is converted from the cellular isoform of prion protein (PrPC)...
  49. Godsave S, Wille H, Pierson J, Prusiner S, Peters P. Plasma membrane invaginations containing clusters of full-length PrPSc are an early form of prion-associated neuropathology in vivo. Neurobiol Aging. 2013;34:1621-31 pubmed publisher
    During prion disease, cellular prion protein (PrP(C)) is refolded into a pathogenic isoform (PrP(Sc)) that accumulates in the central nervous system and causes neurodegeneration and death...
  50. Stella R, Massimino M, Sandri M, Sorgato M, Bertoli A. Cellular prion protein promotes regeneration of adult muscle tissue. Mol Cell Biol. 2010;30:4864-76 pubmed publisher
    It is now well established that the conversion of the cellular prion protein, PrP(C), into its anomalous conformer, PrP(Sc), is central to the onset of prion disease...
  51. Mallucci G, White M, Farmer M, Dickinson A, Khatun H, Powell A, et al. Targeting cellular prion protein reverses early cognitive deficits and neurophysiological dysfunction in prion-infected mice. Neuron. 2007;53:325-35 pubmed
    ..However, we previously showed that targeting endogenous neuronal prion protein (PrP(C)) (the precursor of its disease-associated isoform, PrP(Sc)) in mice with early prion infection reversed ..
  52. Gaspersic J, Hafner Bratkovic I, Stephan M, Veranic P, Bencina M, Vorberg I, et al. Tetracysteine-tagged prion protein allows discrimination between the native and converted forms. FEBS J. 2010;277:2038-50 pubmed publisher
    The conformational conversion of prion protein (PrP) from a native conformation to the amyloid form is a hallmark of transmissible spongiform encephalopathies...
  53. Roffe M, Beraldo F, Bester R, Nunziante M, Bach C, Mancini G, et al. Prion protein interaction with stress-inducible protein 1 enhances neuronal protein synthesis via mTOR. Proc Natl Acad Sci U S A. 2010;107:13147-52 pubmed publisher
    ..spongiform encephalopathies are fatal neurodegenerative diseases caused by the conversion of prion protein (PrP(C)) into an infectious isoform (PrP(Sc)). How this event leads to pathology is not fully understood...
  54. 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
    ..We suggest that prions themselves are not neurotoxic but catalyse the formation of such species from PrP(C)...
  55. Turnbaugh J, Westergard L, Unterberger U, Biasini E, Harris D. The N-terminal, polybasic region is critical for prion protein neuroprotective activity. PLoS ONE. 2011;6:e25675 pubmed publisher
    Several lines of evidence suggest that the normal form of the prion protein, PrP(C), exerts a neuroprotective activity against cellular stress or toxicity...
  56. Herbst A, Banser P, Velasquez C, Mays C, Sim V, Westaway D, et al. Infectious prions accumulate to high levels in non proliferative C2C12 myotubes. PLoS Pathog. 2013;9:e1003755 pubmed publisher
    ..are driven by the strain-specific, template-dependent transconformation of the normal cellular prion protein (PrP(C)) into a disease specific isoform PrP(Sc)...
  57. Wang F, Wang X, Yuan C, Ma J. Generating a prion with bacterially expressed recombinant prion protein. Science. 2010;327:1132-5 pubmed publisher
    The prion hypothesis posits that a misfolded form of prion protein (PrP) is responsible for the infectivity of prion disease...
  58. Li A, Barmada S, Roth K, Harris D. N-terminally deleted forms of the prion protein activate both Bax-dependent and Bax-independent neurotoxic pathways. J Neurosci. 2007;27:852-9 pubmed
    Transgenic (Tg) mice expressing prion protein (PrP) with a deletion of the flexible, N-terminal tail encompassing residues 32-134 spontaneously develop ataxia, degeneration of cerebellar granule cells, and vacuolation of white matter in ..
  59. Meotti F, Carqueja C, Gadotti V, Tasca C, Walz R, Santos A. Involvement of cellular prion protein in the nociceptive response in mice. Brain Res. 2007;1151:84-90 pubmed
    ..Here we investigated the putative involvement of the PrP(c) function on the nociceptive response using PrP(c) null (Prnp(0/0)) and wild-type (Prnp(+/+)) mice submitted to thermal and chemical models of nociception...
  60. Leliveld S, Stitz L, Korth C. Expansion of the octarepeat domain alters the misfolding pathway but not the folding pathway of the prion protein. Biochemistry. 2008;47:6267-78 pubmed publisher
    A misfolded conformation of the prion protein (PrP), PrP (Sc), is the essential component of prions, the infectious agents that cause transmissible neurodegenerative diseases...
  61. Dossena S, Imeri L, Mangieri M, Garofoli A, Ferrari L, Senatore A, et al. Mutant prion protein expression causes motor and memory deficits and abnormal sleep patterns in a transgenic mouse model. Neuron. 2008;60:598-609 pubmed publisher
    A familial form of Creutzfeldt-Jakob disease (CJD) is linked to the D178N/V129 prion protein (PrP) mutation...
  62. Qin K, Zhao L, Ash R, McDonough W, Zhao R. ATM-mediated transcriptional elevation of prion in response to copper-induced oxidative stress. J Biol Chem. 2009;284:4582-93 pubmed publisher
    Increasing evidence suggests that the cellular prion protein (PrP(C)) plays a protective role in response to oxidative stress, but the molecular mechanism is unclear...
  63. Hajj G, Santos T, Cook Z, Martins V. Developmental expression of prion protein and its ligands stress-inducible protein 1 and vitronectin. J Comp Neurol. 2009;517:371-84 pubmed publisher
    Prion protein (PrP(C)) is the normal isoform of PrP(Sc), a protein involved in neurodegenerative disorders...
  64. Hu W, Nessler S, Hemmer B, Eagar T, Kane L, Leliveld S, et al. Pharmacological prion protein silencing accelerates central nervous system autoimmune disease via T cell receptor signalling. Brain. 2010;133:375-88 pubmed publisher
    ..Our data identify cellular prion protein as a regulator of cellular immunological homoeostasis and suggest cellular prion protein as a novel potential target for therapeutic immunomodulation...
  65. Young R, Passet B, Vilotte M, Cribiu E, Beringue V, Le Provost F, et al. The prion or the related Shadoo protein is required for early mouse embryogenesis. FEBS Lett. 2009;583:3296-300 pubmed publisher
    The prion protein PrP has a key role in transmissible spongiform encephalopathies but its biological function remains largely unknown. Recently, a related protein, Shadoo, was discovered...
  66. Kang Y, Zhao X, Lovaas J, Eisenberg E, Greene L. Clathrin-independent internalization of normal cellular prion protein in neuroblastoma cells is associated with the Arf6 pathway. J Cell Sci. 2009;122:4062-9 pubmed publisher
    To understand the role of clathrin-mediated endocytosis in the internalization of normal cellular prion protein (PrP(c)) in neuronal cells, N2a cells were depleted of clathrin by RNA interference...
  67. Watt N, Taylor D, Kerrigan T, Griffiths H, Rushworth J, Whitehouse I, et al. Prion protein facilitates uptake of zinc into neuronal cells. Nat Commun. 2012;3:1134 pubmed publisher
    ..These data suggest that alterations in the cellular prion protein-mediated zinc uptake may contribute to neurodegeneration in prion and other neurodegenerative diseases...
  68. Hizume M, Kobayashi A, Teruya K, Ohashi H, Ironside J, Mohri S, et al. Human prion protein (PrP) 219K is converted to PrPSc but shows heterozygous inhibition in variant Creutzfeldt-Jakob disease infection. J Biol Chem. 2009;284:3603-9 pubmed publisher
    Prion protein gene (PRNP) E219K is a human polymorphism commonly occurring in Asian populations but is rarely found in patients with sporadic Creutzfeldt-Jakob disease (CJD)...
  69. Watts J, Drisaldi B, Ng V, Yang J, Strome B, Horne P, et al. The CNS glycoprotein Shadoo has PrP(C)-like protective properties and displays reduced levels in prion infections. EMBO J. 2007;26:4038-50 pubmed
    ..In Prnp(0/0) CGNs, Sho transgenes were PrP(C)-like in their ability to counteract neurotoxic effects of either Doppel or ..
  70. 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
    Amyloid-beta (A?) oligomers are thought to trigger Alzheimer's disease pathophysiology. Cellular prion protein (PrP(C)) selectively binds oligomeric A? and can mediate Alzheimer's disease-related phenotypes...
  71. Le Pichon C, Firestein S. Expression and localization of the prion protein PrP(C) in the olfactory system of the mouse. J Comp Neurol. 2008;508:487-99 pubmed publisher
    The normal physiological function of the prion protein PrP(C) remains elusive despite its widespread expression, particularly throughout the nervous system...
  72. 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
    Cellular prion protein (PrP(c)) undergoes a disintegrin-mediated physiological cleavage, generating a soluble amino-terminal fragment (N1), the function of which remained unknown...
  73. Senatore A, Colleoni S, Verderio C, Restelli E, Morini R, Condliffe S, et al. Mutant PrP suppresses glutamatergic neurotransmission in cerebellar granule neurons by impairing membrane delivery of VGCC ?(2)?-1 Subunit. Neuron. 2012;74:300-13 pubmed publisher
    How mutant prion protein (PrP) leads to neurological dysfunction in genetic prion diseases is unknown. Tg(PG14) mice synthesize a misfolded mutant PrP which is partially retained in the neuronal endoplasmic reticulum (ER)...
  74. Nuvolone M, Kana V, Hutter G, Sakata D, Mortin Toth S, Russo G, et al. SIRP? polymorphisms, but not the prion protein, control phagocytosis of apoptotic cells. J Exp Med. 2013;210:2539-52 pubmed publisher
    b>Prnp(-/-) mice lack the prion protein PrP(C) and are resistant to prion infections, but variable phenotypes have been reported in Prnp(-/-) mice and the physiological function of PrP(C) remains poorly understood...
  75. Paterson A, Curtis J, Macleod N. Complex I specific increase in superoxide formation and respiration rate by PrP-null mouse brain mitochondria. J Neurochem. 2008;105:177-91 pubmed
    ..free radicals, we have examined mitochondrial free radical production in relation to oxidative phosphorylation in PrP-null mice...
  76. Ratte S, Vreugdenhil M, Boult J, Patel A, Asante E, Collinge J, et al. Threshold for epileptiform activity is elevated in prion knockout mice. Neuroscience. 2011;179:56-61 pubmed publisher
    Prion protein (PrP) is abundant in the nervous system, but its role remains uncertain. Prion diseases depend on an aggregation of the protein that is likely to interfere with its normal function...
  77. Benvegnù S, Roncaglia P, Agostini F, Casalone C, Corona C, Gustincich S, et al. Developmental influence of the cellular prion protein on the gene expression profile in mouse hippocampus. Physiol Genomics. 2011;43:711-25 pubmed publisher
    ..5-day-old) and adult (3-mo-old) mice, both from wild-type and Prnp(0/0) animals...
  78. Gourdain P, Gregoire S, Iken S, Bachy V, Dorban G, Chaigneau T, et al. Adoptive transfer of T lymphocytes sensitized against the prion protein attenuates prion invasion in scrapie-infected mice. J Immunol. 2009;183:6619-28 pubmed publisher
    ..In this study, lymphocytes sensitized against the prion protein in nontolerant Prnp(-/-) mice were transferred into histocompatible wild-type recipients which were partly or totally devoid of their ..
  79. Singh A, Kong Q, Luo X, Petersen R, Meyerson H, Singh N. Prion protein (PrP) knock-out mice show altered iron metabolism: a functional role for PrP in iron uptake and transport. PLoS ONE. 2009;4:e6115 pubmed publisher
    Despite overwhelming evidence implicating the prion protein (PrP) in prion disease pathogenesis, the normal function of this cell surface glycoprotein remains unclear...
  80. Baumann F, Pahnke J, Radovanovic I, Rülicke T, Bremer J, Tolnay M, et al. Functionally relevant domains of the prion protein identified in vivo. PLoS ONE. 2009;4:e6707 pubmed publisher
    The prion consists essentially of PrP(Sc), a misfolded and aggregated conformer of the cellular protein PrP(C)...
  81. Wille H, Bian W, McDonald M, Kendall A, Colby D, Bloch L, et al. Natural and synthetic prion structure from X-ray fiber diffraction. Proc Natl Acad Sci U S A. 2009;106:16990-5 pubmed publisher
    A conformational isoform of the mammalian prion protein (PrP(Sc)) is the sole component of the infectious pathogen that causes the prion diseases...
  82. Watts J, Stöhr J, Bhardwaj S, Wille H, Oehler A, Dearmond S, et al. Protease-resistant prions selectively decrease Shadoo protein. PLoS Pathog. 2011;7:e1002382 pubmed publisher
    The central event in prion diseases is the conformational conversion of the cellular prion protein (PrP(C)) into PrP(Sc), a partially protease-resistant and infectious conformer...
  83. Christensen H, Harris D. A deleted prion protein that is neurotoxic in vivo is localized normally in cultured cells. J Neurochem. 2009;108:44-56 pubmed publisher
    The prion protein (PrP) possesses sequence-specific domains that endow the molecule with neuroprotective and neurotoxic activities, and that may contribute to the pathogenesis of prion diseases...
  84. Tremblay P, Bouzamondo Bernstein E, Heinrich C, Prusiner S, Dearmond S. Developmental expression of PrP in the post-implantation embryo. Brain Res. 2007;1139:60-7 pubmed
    ..tet vector correlate well with the PrP transgene copy, we constructed Prnp-LacZ Tg animals expressing beta-galactosidase that was inserted into the CosSHa.tet vector. The CosSHa...
  85. Powell A, Toescu E, Collinge J, Jefferys J. Alterations in Ca2+-buffering in prion-null mice: association with reduced afterhyperpolarizations in CA1 hippocampal neurons. J Neurosci. 2008;28:3877-86 pubmed publisher
    ..Despite its evolutionary conservation, its normal function remains controversial. PrP-deficient (Prnp(0/0)) mice have weaker afterhyperpolarizations (AHPs) in cerebellar and hippocampal neurons...
  86. 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
    ..This effect was mimicked by, and was not additive with, genetic ablation of cellular prion protein (PrP(C)), a key copper-binding protein in the CNS...
  87. Steinacker P, Hawlik A, Lehnert S, Jahn O, Meier S, Görz E, et al. Neuroprotective function of cellular prion protein in a mouse model of amyotrophic lateral sclerosis. Am J Pathol. 2010;176:1409-20 pubmed publisher
    ..We used the SOD1G93A mouse in a cross-breeding strategy to study the function of physiological prion protein (Prp)...
  88. Mitteregger G, Vosko M, Krebs B, Xiang W, Kohlmannsperger V, Nölting S, et al. The role of the octarepeat region in neuroprotective function of the cellular prion protein. Brain Pathol. 2007;17:174-83 pubmed
    ..We used wild-type mice, PrP knockout (Prnp(-/-)) animals and transgenic mice that lack the octarepeat region (C4/-) and subjected them to controlled ischemia...