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Review

Immunotherapy for Prion Diseases: Opportunities and Obstacles

Li Li1 University of British Columbia & Vancouver Coastal Health Research Institute, Vancouver, British ColumbiaV5Z 3P1, Canada
,
Scott Napper1 University of British Columbia & Vancouver Coastal Health Research Institute, Vancouver, British ColumbiaV5Z 3P1, Canada
&
Neil R Cashman2 Vaccine & Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E3, Canada;3 Brain Research Centre, Rm F137, UBC Hospital, 2211 Wesbrook Mall, Vancouver British Columbia V6T2B5, Canada. Tel.: +1 604 822 2135 Fax: +1 604 822 [email protected]
Pages 269-282 | Published online: 05 Mar 2010

Bibliography

  • Silveira JR , CaugheyB, BaronGS: Prion protein and the molecular features of transmissible spongiform encephalopathy agents.Curr. Top. Microbiol. Immunol.284 , 1–50 (2004).
  • Prusiner SB : Prions.Proc. Natl Acad. Sci. USA95(23) , 13363–13383 (1998).
  • Collinge J : Prion diseases of humans and animals: their causes and molecular basis.Annu. Rev. Neurosci.24 , 519–550 (2001).
  • Beekes M : Prions and prion diseases.FEBS J.274(3) , 575 (2007).
  • Will RG , IronsideJW, ZeidlerMet al.: A new variant of Creutzfeldt–Jakob disease in the UK.Lancet347(9006) , 921–925 (1996).
  • Bruce ME , WillRG, IronsideJWet al.: Transmissions to mice indicate that ‘new variant‘ CJD is caused by the BSE agent.Nature389(6650) , 498–501 (1997).
  • Hill AF , DesbruslaisM, JoinerSet al.: The same prion strain causes vCJD and BSE.Nature389(6650) , 448–450, 526 (1997).
  • Wilesmith JW , WellsGA, CranwellMP, RyanJB: Bovine spongiform encephalopathy: epidemiological studies.Vet. Rec.123(25) , 638–644 (1988).
  • Donnelly CA , FergusonNM, GhaniAC, AndersonRM: Implications of BSE infection screening data for the scale of the British BSE epidemic and current European infection levels.Proc. Biol. Sci.269(1506) , 2179–2190 (2002).
  • Wisniewski T , SigurdssonEM: Therapeutic approaches for prion and Alzheimer‘s diseases.FEBS J.274(15) , 3784–3798 (2007).
  • Collinge J , WhitfieldJ, MckintoshEet al.: Kuru in the 21st Century – an acquired human prion disease with very long incubation periods.Lancet367(9528) , 2068–2074 (2006).
  • Llewelyn CA , HewittPE, KnightRSet al.: Possible transmission of variant Creutzfeldt–Jakob disease by blood transfusion.Lancet363(9407) , 417–421 (2004).
  • Peden AH , HeadMW, RitchieDL, BellJE, IronsideJW: Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient.Lancet364(9433) , 527–529 (2004).
  • Wadsworth JD , JoinerS, HillAFet al.: Tissue distribution of protease resistant prion protein in variant Creutzfeldt–Jakob disease using a highly sensitive immunoblotting assay.Lancet358(9277) , 171–180 (2001).
  • Hilton DA : Pathogenesis and prevalence of variant Creutzfeldt–Jakob disease.J. Pathol.208(2) , 134–141 (2006).
  • Brown P , BrandelJP, PreeceM, SatoT: Iatrogenic Creutzfeldt–Jakob disease: the waning of an era.Neurology67(3) , 389–393 (2006).
  • Health Protection Agency: vCJD abnormal prion protein found in a patient with haemophilia at post mortem. Press release 17 February 2009.
  • Brown P , BradleyR: 1755 and all that: a historical primer of transmissible spongiform encephalopathy.Br. Med. J.317(7174) , 1688–1692 (1998).
  • Conner MM , EbingerMR, BlanchongJA, CrossPC: Infectious disease in cervids of north america: data, models, and management challenges.Ann. NY Acad. Sci.1134 , 146–172 (2008).
  • Williams ES , YoungS: Chronic wasting disease of captive mule deer: a spongiform encephalopathy.J. Wildl. Dis.16(1) , 89–98 (1980).
  • Williams ES , MillerMW: Chronic wasting disease in deer and elk in North America.Rev. Sci. Tech.21(2) , 305–316 (2002).
  • Marsh RF , KincaidAE, BessenRA, BartzJC: Interspecies transmission of chronic wasting disease prions to squirrel monkeys (Saimiri sciureus).J. Virol.79(21) , 13794–13796 (2005).
  • Tamguney G , GilesK, Bouzamondo-BernsteinEet al.: Transmission of elk and deer prions to transgenic mice.J. Virol.80(18) , 9104–9114 (2006).
  • Belay ED , GambettiP, SchonbergerLBet al.: Creutzfeldt–Jakob disease in unusually young patients who consumed venison.Arch. Neurol.58(10) , 1673–1678 (2001).
  • Liberski PP , GuiroyDC, WilliamsES, WalisA, BudkaH: Deposition patterns of disease-associated prion protein in captive mule deer brains with chronic wasting disease.Acta Neuropathol.102(5) , 496–500 (2001).
  • Williams E , MillerM, KreegerT, KahnR, ThorneT: Chronic wasting disease of deer and elk: a review with recommendations for management.J. Wildl. Manage.66(3) , 551–563 (2002).
  • Hamir AN , KunkleRA, CutlipRCet al.: Experimental transmission of chronic wasting disease agent from mule deer to cattle by the intracerebral route.J. Vet. Diagn. Invest.17(3) , 276–281 (2005).
  • Hamir AN , MillerJM, KunkleRA, HallSM, RichtJA: Susceptibility of cattle to first-passage intracerebral inoculation with chronic wasting disease agent from white-tailed deer.Vet. Pathol.44(4) , 487–493 (2007).
  • Williams ES : Scrapie and chronic wasting disease.Clin. Lab. Med.23(1) , 139–159 (2003).
  • Belay ED , MaddoxRA, WilliamsES, MillerMW, GambettiP, SchonbergerLB: Chronic wasting disease and potential transmission to humans.Emerging Infect. Dis.10(6) , 977–984 (2004).
  • Li L , CoulthartMB, BalachandranA, ChakrabarttyA, CashmanNR: Species barriers for chronic wasting disease by in vitro conversion of prion protein.Biochem. Biophys. Res. Commun.364(4) , 796–800 (2007).
  • Prusiner SB : Novel proteinaceous infectious particles cause scrapie.Science216(4542) , 136–144 (1982).
  • Griffith JS : Self-replication and scrapie.Nature215(5105) , 1043–1044 (1967).
  • Kocisko DA , ComeJH, PriolaSAet al.: Cell-free formation of protease-resistant prion protein.Nature370(6489) , 471–474 (1994).
  • Bessen RA , KociskoDA, RaymondGJ, NandanS, LansburyPT, CaugheyB: Non-genetic propagation of strain-specific properties of scrapie prion protein.Nature375(6533) , 698–700 (1995).
  • Saborio GP , PermanneB, SotoC: Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding.Nature411(6839) , 810–813 (2001).
  • Bendheim PE , BrownHR, RudelliRDet al.: Nearly ubiquitous tissue distribution of the scrapie agent precursor protein.Neurology42(1) , 149–156 (1992).
  • Pan KM , BaldwinM, NguyenJet al.: Conversion of α-helices into β-sheets features in the formation of the scrapie prion proteins.Proc. Natl Acad. Sci. USA90(23) , 10962–10966 (1993).
  • Meyer RK , MckinleyMP, BowmanKA, BraunfeldMB, BarryRA, PrusinerSB: Separation and properties of cellular and scrapie prion proteins.Proc. Natl Acad. Sci. USA83(8) , 2310–2314 (1986).
  • Oesch B , WestawayD, WalchliMet al.: A cellular gene encodes scrapie PrP 27–30 protein.Cell40(4) , 735–746 (1985).
  • Caughey BW , DongA, BhatKS, ErnstD, HayesSF, CaugheyWS: Secondary structure analysis of the scrapie-associated protein PrP 27–30 in water by infrared spectroscopy.Biochemistry30(31) , 7672–7680 (1991).
  • Safar J , RollerPP, GajdusekDC, GibbsCJ Jr: Conformational transitions, dissociation, and unfolding of scrapie amyloid (prion) protein. J. Biol. Chem.268(27) , 20276–20284 (1993).
  • Bessen RA , MarshRF: Distinct PrP properties suggest the molecular basis of strain variation in transmissible mink encephalopathy.J. Virol.68(12) , 7859–7868 (1994).
  • Lasmezas CI , DeslysJP, RobainOet al.: Transmission of the BSE agent to mice in the absence of detectable abnormal prion protein.Science275(5298) , 402–405 (1997).
  • Caughey B , KociskoDA, RaymondGJ, LansburyPT Jr: Aggregates of scrapie-associated prion protein induce the cell-free conversion of protease-sensitive prion protein to the protease-resistant state. Chem. Biol.2(12) , 807–817 (1995).
  • Safar J , WilleH, ItriVet al.: Eight prion strains have PrP(Sc) molecules with different conformations.Nat. Med.4(10) , 1157–1165 (1998).
  • Caughey B , RaymondGJ, KociskoDA, LansburyPT Jr: Scrapie infectivity correlates with converting activity, protease resistance, and aggregation of scrapie-associated prion protein in guanidine denaturation studies. J. Virol.71(5) , 4107–4110 (1997).
  • Chiesa R , DrisaldiB, QuaglioEet al.: Accumulation of protease-resistant prion protein (PrP) and apoptosis of cerebellar granule cells in transgenic mice expressing a PrP insertional mutation.Proc. Natl Acad. Sci. USA97(10) , 5574–5579 (2000).
  • Manson JC , JamiesonE, BaybuttHet al.: A single amino acid alteration (101l) introduced into murine PrP dramatically alters incubation time of transmissible spongiform encephalopathy.EMBO J.18(23) , 6855–6864 (1999).
  • Tremblay P , BallHL, KanekoKet al.: Mutant PrPSc conformers induced by a synthetic peptide and several prion strains.J. Virol.78(4) , 2088–2099 (2004).
  • Legname G , BaskakovIV, NguyenHOet al.: Synthetic mammalian prions.Science305(5684) , 673–676 (2004).
  • Bueler H , AguzziA, SailerAet al.: Mice devoid of PrP are resistant to scrapie.Cell73(7) , 1339–1347 (1993).
  • Cashman NR , CaugheyB: Prion diseases – close to effective therapy?Nat. Rev. Drug Discov.3(10) , 874–884 (2004).
  • Griffin JK , CashmanNR: Progress in prion vaccines and immunotherapies.Expert Opin. Biol. Ther.5(1) , 97–110 (2005).
  • Heggebo R , PressCM, GunnesGet al.: Distribution of prion protein in the ileal peyer‘s patch of scrapie-free lambs and lambs naturally and experimentally exposed to the scrapie agent.J. Gen. Virol.81(9) , 2327–2337 (2000).
  • Terry LA , MarshS, RyderSJ, HawkinsSA, WellsGA, SpencerYI: Detection of disease-specific PrP in the distal ileum of cattle exposed orally to the agent of bovine spongiform encephalopathy.Vet. Rec.152(13) , 387–392 (2003).
  • Bons N , Mestre-FrancesN, BelliP, CathalaF, GajdusekDC, BrownP: Natural and experimental oral infection of nonhuman primates by bovine spongiform encephalopathy agents.Proc. Natl Acad. Sci. USA96(7) , 4046–4051 (1999).
  • Sigurdson CJ , SprakerTR, MillerMW, OeschB, HooverEA: PrP(CWD) in the myenteric plexus, vagosympathetic trunk and endocrine glands of deer with chronic wasting disease.J. Gen. Virol.82(Part 10) , 2327–2334 (2001).
  • Mabbott NA , BruceME: The immunobiology of TSE diseases.J. Gen. Virol.82(Part 10) , 2307–2318 (2001).
  • Andreoletti O , BerthonP, MarcDet al.: Early accumulation of PrP(Sc) in gut-associated lymphoid and nervous tissues of susceptible sheep from a Romanov flock with natural scrapie.J. Gen. Virol.81(12) , 3115–3126 (2000).
  • Beekes M , McbridePA: Early accumulation of pathological PrP in the enteric nervous system and gut-associated lymphoid tissue of hamsters orally infected with scrapie.Neurosci. Lett.278(3) , 181–184 (2000).
  • Bruce ME , McconnellI, WillRG, IronsideJW: Detection of variant Creutzfeldt–Jakob disease infectivity in extraneural tissues.Lancet358(9277) , 208–209 (2001).
  • Bruce ME , BrownKL, MabbottNA, FarquharCF, JeffreyM: Follicular dendritic cells in TSE pathogenesis.Immunol. Today21(9) , 442–446 (2000).
  • Kitamoto T , MuramotoT, MohriS, Doh-UraK, TateishiJ: Abnormal isoform of prion protein accumulates in follicular dendritic cells in mice with Creutzfeldt–Jakob disease.J. Virol.65(11) , 6292–6295 (1991).
  • Mcbride PA , EikelenboomP, KraalG, FraserH, BruceME: PrP protein is associated with follicular dendritic cells of spleens and lymph nodes in uninfected and scrapie-infected mice.J. Pathol.168(4) , 413–418 (1992).
  • Brown KL , StewartK, RitchieDLet al.: Scrapie replication in lymphoid tissues depends on prion protein-expressing follicular dendritic cells.Nat. Med.5(11) , 1308–1312 (1999).
  • Montrasio F , FriggR, GlatzelMet al.: Impaired prion replication in spleens of mice lacking functional follicular dendritic cells.Science288(5469) , 1257–1259 (2000).
  • Mabbott NA , MackayF, MinnsF, BruceME: Temporary inactivation of follicular dendritic cells delays neuroinvasion of scrapie.Nat. Med.6(7) , 719–720 (2000).
  • Jeffrey M , McgovernG, GoodsirCM, BrownKL, BruceME: Sites of prion protein accumulation in scrapie-infected mouse spleen revealed by immuno-electron microscopy.J. Pathol.191(3) , 323–332 (2000).
  • Klein MA , FriggR, FlechsigEet al.: A crucial role for B cells in neuroinvasive scrapie.Nature390(6661) , 687–690 (1997).
  • Eklund CM , KennedyRC, HadlowWJ: Pathogenesis of scrapie virus infection in the mouse.J. Infect. Dis.117(1) , 15–22 (1967).
  • Fraser H , DickinsonAG: Pathogenesis of scrapie in the mouse: the role of the spleen.Nature226(5244) , 462–463 (1970).
  • Fraser H , DickinsonAG: Studies of the lymphoreticular system in the pathogenesis of scrapie: the role of spleen and thymus.J. Comp. Pathol.88(4) , 563–573 (1978).
  • Haik S , FaucheuxBA, HauwJJ: Brain targeting through the autonomous nervous system: lessons from prion diseases.Trends Mol. Med.10(3) , 107–112 (2004).
  • Glatzel M , HeppnerFL, AlbersKM, AguzziA: Sympathetic innervation of lymphoreticular organs is rate limiting for prion neuroinvasion.Neuron31(1) , 25–34 (2001).
  • Kingsbury DT , SmeltzerDA, GibbsCJ Jr, Gajdusek DC: Evidence for normal cell-mediated immunity in scrapie-infected mice. Infect. Immun.32(3) , 1176–1180 (1981).
  • Aucouturier P , CarpRI, CarnaudC, WisniewskiT: Prion diseases and the immune system.Clin. Immunol.96(2) , 79–85 (2000).
  • Porter DD , PorterHG, CoxNA: Failure to demonstrate a humoral immune response to scrapie infection in mice.J. Immunol.111(5) , 1407–1410 (1973).
  • Solforosi L , BellonA, SchallerM, CruiteJT, AbalosGC, WilliamsonRA: Toward molecular dissection of PrPC-PrPSc interactions.J. Biol. Chem.282(10) , 7465–7471 (2007).
  • Ma J , LindquistS: Conversion of PrP to a self-perpetuating PrPSc-like conformation in the cytosol.Science298(5599) , 1785–1788 (2002).
  • Feraudet C , MorelN, SimonSet al.: Screening of 145 anti-PrP monoclonal antibodies for their capacity to inhibit PrPSc replication in infected cells.J. Biol. Chem.280(12) , 11247–11258 (2005).
  • Caughey B , RaymondGJ: The scrapie-associated form of PrP is made from a cell surface precursor that is both protease- and phospholipase-sensitive.J. Biol. Chem.266(27) , 18217–18223 (1991).
  • Borchelt DR , ScottM, TaraboulosA, StahlN, PrusinerSB: Scrapie and cellular prion proteins differ in their kinetics of synthesis and topology in cultured cells.J. Cell Biol.110(3) , 743–752 (1990).
  • Kascsak RJ , RubensteinR, MerzPAet al.: Mouse polyclonal and monoclonal antibody to scrapie-associated fibril proteins.J. Virol.61(12) , 3688–3693 (1987).
  • Gabizon R , MckinleyMP, GrothD, PrusinerSB: Immunoaffinity purification and neutralization of scrapie prion infectivity.Proc. Natl Acad. Sci. USA85(18) , 6617–6621 (1988).
  • Horiuchi M , CaugheyB: Specific binding of normal prion protein to the scrapie form via a localized domain initiates its conversion to the protease-resistant state.EMBO J.18(12) , 3193–3203 (1999).
  • Korth C , StierliB, StreitPet al.: Prion (PrPSc)-specific epitope defined by a monoclonal antibody.Nature390(6655) , 74–77 (1997).
  • Enari M , FlechsigE, WeissmannC: Scrapie prion protein accumulation by scrapie-infected neuroblastoma cells abrogated by exposure to a prion protein antibody.Proc. Natl Acad. Sci. USA98(16) , 9295–9299 (2001).
  • Peretz D , WilliamsonRA, KanekoKet al.: Antibodies inhibit prion propagation and clear cell cultures of prion infectivity.Nature412(6848) , 739–743 (2001).
  • Demart S , FournierJG, CreminonCet al.: New insight into abnormal prion protein using monoclonal antibodies.Biochem. Biophys. Res. Commun.265(3) , 652–657 (1999).
  • Perrier V , SolassolJ, CrozetCet al.: Anti-PrP antibodies block PrPSc replication in prion-infected cell cultures by accelerating PrPC degradation.J. Neurochem.89(2) , 454–463 (2004).
  • Hundt C , PeyrinJM, HaikSet al.: Identification of interaction domains of the prion protein with its 37-kDa/67-kDa laminin receptor.EMBO J.20(21) , 5876–5886 (2001).
  • Kim CL , UmetaniA, MatsuiT, IshiguroN, ShinagawaM, HoriuchiM: Antigenic characterization of an abnormal isoform of prion protein using a new diverse panel of monoclonal antibodies.Virology320(1) , 40–51 (2004).
  • Kim CL , KarinoA, IshiguroN, ShinagawaM, SatoM, HoriuchiM: Cell-surface retention of PrPC by anti-PrP antibody prevents protease-resistant PrP formation.J. Gen. Virol.85(Part 11) , 3473–3482 (2004).
  • Cardinale A , FilesiI, VetrugnoV, PocchiariM, SyMS, BioccaS: Trapping prion protein in the endoplasmic reticulum impairs PrPC maturation and prevents PrPSc accumulation.J. Biol. Chem.280(1) , 685–694 (2005).
  • Vetrugno V , CardinaleA, FilesiIet al.: KDEL-tagged anti-prion intrabodies impair PrP lysosomal degradation and inhibit scrapie infectivity.Biochem. Biophys. Res. Commun.338(4) , 1791–1797 (2005).
  • Polymenidou M , HeppnerFL, PellicioliECet al.: Humoral immune response to native eukaryotic prion protein correlates with anti-prion protection.Proc. Natl Acad. Sci. USA101(Suppl. 2) , 14670–14676 (2004).
  • Sigurdsson EM , SyMS, LiRet al.: Anti-prion antibodies for prophylaxis following prion exposure in mice.Neurosci. Lett.336(3) , 185–187 (2003).
  • White AR , EneverP, TayebiMet al.: Monoclonal antibodies inhibit prion replication and delay the development of prion disease.Nature422(6927) , 80–83 (2003).
  • Jackson GS , HosszuLL, PowerAet al.: Reversible conversion of monomeric human prion protein between native and fibrilogenic conformations.Science283(5409) , 1935–1937 (1999).
  • Khalili-Shirazi A , QuaratinoS, LondeiMet al.: Protein conformation significantly influences immune responses to prion protein.J. Immunol.174(6) , 3256–3263 (2005).
  • Koller MF , GrauT, ChristenP: Induction of antibodies against murine full-length prion protein in wild-type mice.J. Neuroimmunol.132(1–2) , 113–116 (2002).
  • Hanan E , GorenO, EshkenazyM, SolomonB: Immunomodulation of the human prion peptide 106–126 aggregation.Biochem. Biophys. Res. Commun.280(1) , 115–120 (2001).
  • Hanan E , PriolaSA, SolomonB: Anti-aggregating antibody raised against human PrP 106–126 recognizes pathological and normal isoforms of the whole prion protein.Cell. Mol. Neurobiol.21(6) , 693–703 (2001).
  • Schwarz A , KratkeO, BurwinkelMet al.: Immunisation with a synthetic prion protein-derived peptide prolongs survival times of mice orally exposed to the scrapie agent.Neurosci. Lett.350(3) , 187–189 (2003).
  • Sigurdsson EM , BrownDR, DanielsMet al.: Immunization delays the onset of prion disease in mice.Am. J. Pathol.161(1) , 13–17 (2002).
  • Souan L , TalY, FellingY, CohenIR, TaraboulosA, MorF: Modulation of proteinase-K resistant prion protein by prion peptide immunization.Eur. J. Immunol.31(8) , 2338–2346 (2001).
  • Arbel M , LavieV, SolomonB: Generation of antibodies against prion protein in wild-type mice via helix 1 peptide immunization.J. Neuroimmunol.144(1–2) , 38–45 (2003).
  • Gilch S , WopfnerF, Renner-MullerIet al.: Polyclonal anti-PrP auto-antibodies induced with dimeric PrP interfere efficiently with PrPSc propagation in prion-infected cells.J. Biol. Chem.278(20) , 18524–18531 (2003).
  • Rosset MB , BalleriniC, GregoireS, MetharomP, CarnaudC, AucouturierP: Breaking immune tolerance to the prion protein using prion protein peptides plus oligodeoxynucleotide-CpG in mice.J. Immunol.172(9) , 5168–5174 (2004).
  • Magri G , ClericiM, Dall‘araPet al.: Decrease in pathology and progression of scrapie after immunisation with synthetic prion protein peptides in hamsters.Vaccine23(22) , 2862–2868 (2005).
  • Nicoll JA , WilkinsonD, HolmesC, SteartP, MarkhamH, WellerRO: Neuropathology of human Alzheimer disease after immunization with amyloid-β peptide: a case report.Nat. Med.9(4) , 448–452 (2003).
  • Goni F , KnudsenE, SchreiberFet al.: Mucosal vaccination delays or prevents prion infection via an oral route.Neuroscience133(2) , 413–421 (2005).
  • White AR , CollinsSJ, MaherFet al.: Prion protein-deficient neurons reveal lower glutathione reductase activity and increased susceptibility to hydrogen peroxide toxicity.Am. J. Pathol.155(5) , 1723–1730 (1999).
  • Gregoire S , BergotAS, FeraudetC, CarnaudC, AucouturierP, RossetMB: The murine B cell repertoire is severely selected against endogenous cellular prion protein.J. Immunol.175(10) , 6443–6449 (2005).
  • Nikles D , BachP, BollerKet al.: Circumventing tolerance to the prion protein (PrP): vaccination with PrP-displaying retrovirus particles induces humoral immune responses against the native form of cellular PrP.J. Virol.79(7) , 4033–4042 (2005).
  • Handisurya A , GilchS, WinterDet al.: Vaccination with prion peptide-displaying papillomavirus-like particles induces autoantibodies to normal prion protein that interfere with pathologic prion protein production in infected cells.FEBS J.274(7) , 1747–1758 (2007).
  • Wuertzer CA , SullivanMA, QiuX, FederoffHJ: CNS delivery of vectored prion-specific single-chain antibodies delays disease onset.Mol. Ther.16(3) , 481–486 (2008).
  • Rosset MB , SacquinA, LecollinetSet al.: Dendritic cell-mediated-immunization with xenogenic PrP and adenoviral vectors breaks tolerance and prolongs mice survival against experimental scrapie.PLoS ONE4(3) , E4917 (2009).
  • Cashman NR , LoertscherR, NalbantogluJet al.: Cellular isoform of the scrapie agent protein participates in lymphocyte activation.Cell61(1) , 185–192 (1990).
  • Mouillet-Richard S , ErmonvalM, ChebassierCet al.: Signal transduction through prion protein.Science289(5486) , 1925–1928 (2000).
  • Parkin ET , WattNT, HussainIet al.: Cellular prion protein regulates β-secretase cleavage of the Alzheimer‘s amyloid precursor protein.Proc. Natl Acad. Sci. USA104(26) , 11062–11067 (2007).
  • Lauren J , GimbelDA, NygaardHB, GilbertJW, StrittmatterSM: Cellular prion protein mediates impairment of synaptic plasticity by amyloid-β oligomers.Nature457(7233) , 1128–1132 (2009).
  • Hooper NM , TurnerAJ: A new take on prions: preventing Alzheimer‘s disease.Trends Biochem. Sci.33(4) , 151–155 (2008).
  • Zou WQ , CashmanNR: Acidic pH and detergents enhance in vitro conversion of human brain PrPC to a PrPSc-like form.J. Biol. Chem.277(46) , 43942–43947 (2002).
  • Paramithiotis E , PinardM, LawtonTet al.: A prion protein epitope selective for the pathologically misfolded conformation.Nat. Med.9(7) , 893–899 (2003).
  • Hedlin PD , CashmanNR, LiLet al.: Design and delivery of a cryptic PrP(C) epitope for induction of PrP(Sc)-specific antibody responses.Vaccine (2009) (Epub ahead of print).

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