Abstract
Prion diseases are a group of invariably fatal and transmissible neurodegenerative disorders that are associated with the misfolding of the normal cellular prion protein, with the misfolded conformers constituting an infectious unit referred to as a “prion”. Prions can spread within an affected organism by directly propagating this misfolding within and between cells and can transmit disease between animals of the same and different species. Prion diseases have a range of clinical phenotypes in humans and animals, with a principle determinant of this attributed to different conformations of the misfolded protein, referred to as prion strains. This chapter will describe the different clinical manifestations of prion diseases, the evidence that these diseases can be transmitted by an infectious protein and how the misfolding of this protein causes disease.
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Abbreviations
- AMPA:
-
α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
- Aβ:
-
Amyloid beta
- BSE:
-
Bovine spongiform encephalopathy
- C1:
-
C-terminal fragment of PrP produced by α-cleavage
- C2:
-
C-terminal fragment of PrP produced by β-cleavage
- C3:
-
C-terminal fragment of PrP produced by γ-cleavage
- Cu2+ :
-
Copper-II ion
- CCL2:
-
Chemokine (Cysteine-cysteine motif) ligand 2
- CCL5:
-
Chemokine (Cysteine-cysteine motif) ligand 5
- CCR2:
-
Cysteine-cysteine chemokine receptor 2
- CCR5:
-
Cysteine-cysteine chemokine receptor 5
- CJD:
-
Creutzfeldt-Jakob disease
- CNS:
-
Central nervous system
- COCS:
-
Cerebellar organotypic cultured slices
- CSF:
-
Cerebrospinal fluid
- CWD:
-
Chronic wasting disease
- D177N:
-
Disease-associated mutation of PrP; aspartic acid at position 177 is replaced by asparagine
- EEG:
-
Electroencephalogram
- eIF2α:
-
Eukaryotic translation factor-2 alpha
- ER:
-
Endoplasmic reticulum
- ERAD:
-
Endoplasmic-reticulum-associated protein degradation
- FFI:
-
Fatal familial insomnia
- FTIR spectroscopy:
-
Fourier transform infrared spectroscopy
- GFAP:
-
Glial fibrillary acidic protein
- GPI:
-
Glycosylphosphatidylinositol
- Grp78/BiP:
-
78 kDa glucose-regulated protein/binding immunoglobulin protein
- GSS:
-
Gerstmann–Sträussler–Scheinker syndrome
- IL-1:
-
Interleukin-1
- IL-10:
-
Interleukin-10
- IL-12p40:
-
Interleukin-12 p40
- IL-1R:
-
Interleukin-1 receptor
- IL-1Ra:
-
Interleukin-1 receptor antagonist
- KA:
-
Kainate
- kDa:
-
Kilodalton
- M:
-
Methionine; MM implies methionine homozygosity at position 129 of PrP
- MAPK:
-
Mitogen-activated protein kinase
- MCP-1:
-
Monocyte chemoattractant protein 1
- MEK:
-
MAPK/ERK kinase
- mGluR:
-
Metabotropic glutamate receptors
- MRI:
-
Magnetic resonance imaging
- mRNA:
-
Messenger RNA
- MV:
-
Implies methionine-valine heterozygosity at position 129 of PrP
- N1:
-
N-terminal fragment of PrP produced by α-cleavage
- N2:
-
N-terminal fragment of PrP produced by β-cleavage
- N2a:
-
Murine neuroblastoma cell line
- N3:
-
N-terminal fragment of PrP produced by γ-cleavage
- NMDAR:
-
N-methyl-d-aspartate receptor
- NMR:
-
Nuclear magnetic resonance spectroscopy
- P101L:
-
Disease-associated mutation of PrP; proline at position 101 is replaced by luecine
- PE:
-
Phosphatidylethanolamine
- PERK:
-
Protein kinase RNA (PKR)-like ER kinase
- PK:
-
Proteinase K
- PMCA:
-
Protein misfolding cyclic amplification
- POPG:
-
1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol
- PRNP :
-
Gene encoding the human prion protein
- Prnp−/− :
-
Prion protein gene knock out animals
- PrP:
-
Prion protein
- PrPC :
-
Normal, cellular PrP
- PrPSc :
-
Disease-associated PrP
- RNA:
-
Ribonucleic acid
- ROS:
-
Reactive oxygen species
- RT-QuIC:
-
Real time quaking induced conversion
- sCJD:
-
Sporadic CJD
- TGFβ:
-
Transforming growth factor beta
- TNFα:
-
Tumour necrosis factor alpha
- UK:
-
United Kingdom
- UPR:
-
Unfolded protein response
- USA:
-
United States of America
- V:
-
Valine; VV implies valine homozygosity at position 129 of PrP
- vCJD:
-
Variant CJD
References
Prusiner SB (1998) Prions. Proc Natl Acad Sci U S A 95(23):13363–13383
Masters CL, Kakulas BA et al (1976) Preclinical lesions and their progression in the experimental spongiform encephalopathies (kuru and Creutzfeldt-Jakob disease) in primates. J Neuropathol Exp Neurol 35(6):593–605
Field EJ, Peat A (1969) Structural changes in scrapieaffected brain. Biochem J 114(2):19P–20P
DeArmond SJ, Mobley WC et al (1987) Changes in the localization of brain prion proteins during scrapie infection. Neurology 37(8):1271–1280
Jaunmuktane Z, Mead S et al (2015) Evidence for human transmission of amyloid-beta pathology and cerebral amyloid angiopathy. Nature 525(7568):247–250
Sacino AN, Brooks M et al (2014) Intramuscular injection of alpha-synuclein induces CNS alpha-synuclein pathology and a rapid-onset motor phenotype in transgenic mice. Proc Natl Acad Sci U S A 111(29):10732–10737
Luk KC, Kehm V et al (2012) Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 338(6109):949–953
Sternbach G, Dibble CL et al (1997) From Creutzfeldt-Jakob disease to the mad cow epidemic. J Emerg Med 15(5):701–705
Brown P, Gibbs CJ Jr et al (1994) Human spongiform encephalopathy: the National Institutes of Health series of 300 cases of experimentally transmitted disease. Ann Neurol 35(5):513–529
Klug GM, Wand H et al (2013) Intensity of human prion disease surveillance predicts observed disease incidence. J Neurol Neurosurg Psychiatry 84(12):1372–1377
Brown P, Cathala F et al (1986) Creutzfeldt-Jakob disease: clinical analysis of a consecutive series of 230 neuropathologically verified cases. Ann Neurol 20(5):597–602
Kovacs GG, Puopolo M et al (2005) Genetic prion disease: the EUROCJD experience. Hum Genet 118(2):166–174
Montagna P, Gambetti P et al (2003) Familial and sporadic fatal insomnia. Lancet Neurol 2(3):167–176
Ghetti B, Dlouhy SR et al (1995) Gerstmann-Straussler-Scheinker disease and the Indiana kindred. Brain Pathol 5(1):61–75
Gajdusek DC, Zigas V (1957) Degenerative disease of the central nervous system in New Guinea; the endemic occurrence of kuru in the native population. N Engl J Med 257(20):974–978
Alpers MP (2008) Review. The epidemiology of kuru: monitoring the epidemic from its peak to its end. Philos Trans R Soc Lond Ser B Biol Sci 363(1510):3707–3713
Bruce ME, Will RG et al (1997) Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent. Nature 389(6650):498–501
Hill AF, Desbruslais M et al (1997) The same prion strain causes vCJD and BSE. Nature 389(6650):448–450. 526
Urwin PJ, Mackenzie JM et al (2015) Creutzfeldt-Jakob disease and blood transfusion: updated results of the UK transfusion medicine epidemiology review study. Vox Sang 110(4):310–316
The National CJD Research & Surveillance Unit Western General Hospital E, EH4 2XU (2014) 23rd annual report 2014. Creutzfeldt-Jakob Disease Surveillance in the UK
Murphy EL, David Connor J et al (2004) Estimating blood donor loss due to the variant CJD travel deferral. Transfusion 44(5):645–650
Diack AB, Head MW et al (2014) Variant CJD. 18 years of research and surveillance. Prion 8(4):286–295
Brown P, Brandel JP et al (2012) Iatrogenic Creutzfeldt-Jakob disease, final assessment. Emerg Infect Dis 18(6):901–907
Lawson VA, Stewart JD et al (2007) Enzymatic detergent treatment protocol that reduces protease-resistant prion protein load and infectivity from surgical-steel monofilaments contaminated with a human-derived prion strain. J Gen Virol 88(Pt 10):2905–2914
Plummer PJ (1946) Scrapie-A disease of sheep: a review of the literature. Can J Comp Med Vet Sci 10(2):49–54
Wells GA, Scott AC et al (1987) A novel progressive spongiform encephalopathy in cattle. Vet Rec 121(18):419–420
Wilesmith JW, Wells GA et al (1988) Bovine spongiform encephalopathy: epidemiological studies. Vet Rec 123(25):638–644
Fraser H, McConnell I et al (1988) Transmission of bovine spongiform encephalopathy to mice. Vet Rec 123(18):472
Wilesmith JW, Ryan JB et al (1992) Bovine spongiform encephalopathy: case-control studies of calf feeding practices and meat and bonemeal inclusion in proprietary concentrates. Res Vet Sci 52(3):325–331
Harman JL, Silva CJ (2009) Bovine spongiform encephalopathy. J Am Vet Med Assoc 234(1):59–72
World Organisation for Animal Health: Number of cases of bovine spongiform encephalopathy (BSE) reported in the United Kingdom. http://www.oie.int/animal-health-in-the-world/bse-specific-data/number-of-cases-in-the-united-kingdom/#Royaume-Uni (2016). Accessed 28th April 2016
Liberski PP, Sikorska B et al (2009) Transmissible mink encephalopathy—review of the etiology of a rare prion disease. Folia Neuropathol 47(2):195–204
Benestad SL, Sarradin P et al (2003) Cases of scrapie with unusual features in Norway and designation of a new type, Nor98. Vet Rec 153(7):202–208
Windl O, Dawson M (2012) Animal prion diseases. Subcell Biochem 65:497–516
Williams ES, Young S (1980) Chronic wasting disease of captive mule deer: a spongiform encephalopathy. J Wildl Dis 16(1):89–98
Spraker TR, Miller MW et al (1997) Spongiform encephalopathy in free-ranging mule deer (Odocoileus hemionus), white-tailed deer (Odocoileus virginianus) and Rocky Mountain elk (Cervus elaphus nelsoni) in northcentral Colorado. J Wildl Dis 33(1):1–6
Miller MW, Williams ES et al (2000) Epizootiology of chronic wasting disease in free-ranging cervids in Colorado and Wyoming. J Wildl Dis 36(4):676–690
Haley NJ, Hoover EA (2015) Chronic wasting disease of cervids: current knowledge and future perspectives. Annu Rev Anim Biosci 3:305–325
Pritzkow S, Morales R et al (2015) Grass plants bind, retain, uptake, and transport infectious prions. Cell Rep 11(8):1168–1175
Mathiason CK, Powers JG et al (2006) Infectious prions in the saliva and blood of deer with chronic wasting disease. Science 314(5796):133–136
Miller MW, Williams ES et al (2004) Environmental sources of prion transmission in mule deer. Emerg Infect Dis 10(6):1003–1006
Balachandran A, Harrington NP et al (2010) Experimental oral transmission of chronic wasting disease to red deer (Cervus elaphus elaphus): early detection and late stage distribution of protease-resistant prion protein. Can Vet J 51(2):169–178
Spraker TR, Zink RR et al (2002) Distribution of protease-resistant prion protein and spongiform encephalopathy in free-ranging mule deer (Odocoileus hemionus) with chronic wasting disease. Vet Pathol 39(5):546–556
Jewell JE, Brown J et al (2006) Prion protein in cardiac muscle of elk (Cervus elaphus nelsoni) and white-tailed deer (Odocoileus virginianus) infected with chronic wasting disease. J Gen Virol 87(Pt 11):3443–3450
Angers RC, Browning SR et al (2006) Prions in skeletal muscles of deer with chronic wasting disease. Science 311(5764):1117
Belay ED, Maddox RA et al (2004) Chronic wasting disease and potential transmission to humans. Emerg Infect Dis 10(6):977–984
Gordon WS (1946) Advances in veterinary research. Vet Rec 58(47):516–525
Cuillé J, Chelle PL (1939) Transmission experimentale de la tremblante a la chevre. Comptes rendus hebdomadaires des sciences de l’Academie des Sciences 208:1058–1060
Chandler RL (1961) Encephalopathy in mice produced by inoculation with scrapie brain material. Lancet 1(7191):1378–1379
Gajdusek DC, Gibbs CJ et al (1966) Experimental transmission of a Kuru-like syndrome to chimpanzees. Nature 209(5025):794–796
Georgsson G, Sigurdarson S et al (2006) Infectious agent of sheep scrapie may persist in the environment for at least 16 years. J Gen Virol 87(Pt 12):3737–3740
Afanasieva EG, Kushnirov VV et al (2011) Interspecies transmission of prions. Biochemistry (Mosc) 76(13):1375–1384
Alper T, Haig DA et al (1966) The exceptionally small size of the scrapie agent. Biochem Biophys Res Commun 22(3):278–284
Alper T, Cramp WA et al (1967) Does the agent of scrapie replicate without nucleic acid? Nature 214(90):764–766
Prusiner SB, Groth DF et al (1980) Molecular properties, partial purification, and assay by incubation period measurements of the hamster scrapie agent. Biochemistry 19(21):4883–4891
Pattison IH, Jones KM (1967) The possible nature of the transmissible agent of scrapie. Vet Rec 80(1):2–9
Prusiner SB (1982) Novel proteinaceous infectious particles cause scrapie. Science 216(4542):136–144
Chesebro B, Race R et al (1985) Identification of scrapie prion protein-specific mRNA in scrapie-infected and uninfected brain. Nature 315(6017):331–333
Stahl N, Borchelt DR et al (1987) Scrapie prion protein contains a phosphatidylinositol glycolipid. Cell 51(2):229–240
Bendheim PE, Brown HR et al (1992) Nearly ubiquitous tissue distribution of the scrapie agent precursor protein. Neurology 42(1):149–156
Wopfner F, Weidenhofer G et al (1999) Analysis of 27 mammalian and 9 avian PrPs reveals high conservation of flexible regions of the prion protein. J Mol Biol 289(5):1163–1178
Yusa S, Oliveira-Martins JB et al (2012) Cellular prion protein: from physiology to pathology. Virus 4(11):3109–3131
Stimson E, Hope J et al (1999) Site-specific characterization of the N-linked glycans of murine prion protein by high-performance liquid chromatography/electrospray mass spectrometry and exoglycosidase digestions. Biochemistry 38(15):4885–4895
Zahn R, Liu A et al (2000) NMR solution structure of the human prion protein. Proc Natl Acad Sci U S A 97(1):145–150
Brown DR, Qin K et al (1997) The cellular prion protein binds copper in vivo. Nature 390(6661):684–687
Schatzl HM, Da Costa M et al (1995) Prion protein gene variation among primates. J Mol Biol 245(4):362–374
Caughey B, Raymond GJ et al (1991) N-terminal truncation of the scrapie-associated form of PrP by lysosomal protease(s): implications regarding the site of conversion of PrP to the protease-resistant state. J Virol 65(12):6597–6603
Chen SG, Teplow DB et al (1995) Truncated forms of the human prion protein in normal brain and in prion diseases. J Biol Chem 270(32):19173–19180
Lewis V, Johanssen VA et al (2016) Prion protein “gamma-cleavage”: characterizing a novel endoproteolytic processing event. Cell Mol Life Sci 73(3):667–683
Altmeppen HC, Prox J et al (2011) Lack of a-disintegrin-and-metalloproteinase ADAM10 leads to intracellular accumulation and loss of shedding of the cellular prion protein in vivo. Mol Neurodegener 6:36
Walmsley AR, Watt NT et al (2009) Alpha-cleavage of the prion protein occurs in a late compartment of the secretory pathway and is independent of lipid rafts. Mol Cell Neurosci 40(2):242–248
McMahon HE, Mange A et al (2001) Cleavage of the amino terminus of the prion protein by reactive oxygen species. J Biol Chem 276(3):2286–2291
Watt NT, Hooper NM (2005) Reactive oxygen species (ROS)-mediated beta-cleavage of the prion protein in the mechanism of the cellular response to oxidative stress. Biochem Soc Trans 33(Pt 5):1123–1125
Haigh CL, Drew SC et al (2009) Dominant roles of the polybasic proline motif and copper in the PrP23-89-mediated stress protection response. J Cell Sci 122(Pt 10):1518–1528
Haigh CL, McGlade AR et al (2015) MEK1 transduces the prion protein N2 fragment antioxidant effects. Cell Mol Life Sci 72(8):1613–1629
Lewis V, Hill AF et al (2009) Increased proportions of C1 truncated prion protein protect against cellular M1000 prion infection. J Neuropathol Exp Neurol 68(10):1125–1135
Westergard L, Turnbaugh JA et al (2011) A naturally occurring C-terminal fragment of the prion protein (PrP) delays disease and acts as a dominant-negative inhibitor of PrPSc formation. J Biol Chem 286(51):44234–44242
Guillot-Sestier MV, Sunyach C et al (2009) The alpha-secretase-derived N-terminal product of cellular prion, N1, displays neuroprotective function in vitro and in vivo. J Biol Chem 284(51):35973–35986
Haigh CL, Lewis VA et al (2009) PrPC-related signal transduction is influenced by copper, membrane integrity and the alpha cleavage site. Cell Res 19(9):1062–1078
Caetano FA, Lopes MH et al (2008) Endocytosis of prion protein is required for ERK1/2 signaling induced by stress-inducible protein 1. J Neurosci 28(26):6691–6702
Bremer J, Baumann F et al (2010) Axonal prion protein is required for peripheral myelin maintenance. Nat Neurosci 13(3):310–318
Aguzzi A, Baumann F et al (2008) The prion’s elusive reason for being. Annu Rev Neurosci 31:439–477
Bakkebo MK, Mouillet-Richard S et al (2015) The cellular prion protein: a player in immunological quiescence. Front Immunol 6:450
Del Rio JA, Gavin R (2016) Functions of the cellular prion protein, the end of Moore’s law, and Ockham’s razor theory. Prion 10(1):25–40
Bueler H, Aguzzi A et al (1993) Mice devoid of PrP are resistant to scrapie. Cell 73(7):1339–1347
Manson JC, Clarke AR et al (1994) PrP gene dosage determines the timing but not the final intensity or distribution of lesions in scrapie pathology. Neurodegeneration 3(4):331–340
Meyer RK, McKinley MP et al (1986) Separation and properties of cellular and scrapie prion proteins. Proc Natl Acad Sci U S A 83(8):2310–2314
Pan KM, Baldwin M et al (1993) Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins. Proc Natl Acad Sci U S A 90(23):10962–10966
Kocisko DA, Come JH et al (1994) Cell-free formation of protease-resistant prion protein. Nature 370(6489):471–474
Hill AF, Antoniou M et al (1999) Protease-resistant prion protein produced in vitro lacks detectable infectivity. J Gen Virol 80(Pt 1):11–14
Saborio GP, Permanne B et al (2001) Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature 411(6839):810–813
Castilla J, Saa P et al (2005) In vitro generation of infectious scrapie prions. Cell 121(2):195–206
Legname G, Baskakov IV et al (2004) Synthetic mammalian prions. Science 305(5684):673–676
Colby DW, Wain R et al (2010) Protease-sensitive synthetic prions. PLoS Pathog 6(1):e1000736
Nazor KE, Kuhn F et al (2005) Immunodetection of disease-associated mutant PrP, which accelerates disease in GSS transgenic mice. EMBO J 24(13):2472–2480
Cappai R, Stewart L et al (1999) Familial prion disease mutation alters the secondary structure of recombinant mouse prion protein: implications for the mechanism of prion formation. Biochemistry 38(11):3280–3284
Hsiao KK, Scott M et al (1990) Spontaneous neurodegeneration in transgenic mice with mutant prion protein. Science 250(4987):1587–1590
Manson JC, Jamieson E et al (1999) A single amino acid alteration (101L) introduced into murine PrP dramatically alters incubation time of transmissible spongiform encephalopathy. EMBO J 18(23):6855–6864
Lawson VA, Lumicisi B et al (2010) Glycosaminoglycan sulphation affects the seeded misfolding of a mutant prion protein. PLoS One 5(8):e12351
Jackson WS, Borkowski AW et al (2009) Spontaneous generation of prion infectivity in fatal familial insomnia knockin mice. Neuron 63(4):438–450
Kim JI, Cali I et al (2010) Mammalian prions generated from bacterially expressed prion protein in the absence of any mammalian cofactors. J Biol Chem 285(19):14083–14087
Zhou Z, Xiao G (2013) Conformational conversion of prion protein in prion diseases. Acta Biochim Biophys Sin Shanghai 45(6):465–476
Deleault NR, Piro JR et al (2012) Isolation of phosphatidylethanolamine as a solitary cofactor for prion formation in the absence of nucleic acids. Proc Natl Acad Sci U S A 109(22):8546–8551
Saleem F, Bjorndahl TC et al (2014) Lipopolysaccharide induced conversion of recombinant prion protein. Prion 8(2):221–232
Wang F, Yin S et al (2010) Role of the highly conserved middle region of prion protein (PrP) in PrP-lipid interaction. Biochemistry 49(37):8169–8176
Deleault NR, Geoghegan JC et al (2005) Protease-resistant prion protein amplification reconstituted with partially purified substrates and synthetic polyanions. J Biol Chem 280(29):26873–26879
Deleault NR, Walsh DJ et al (2012) Cofactor molecules maintain infectious conformation and restrict strain properties in purified prions. Proc Natl Acad Sci U S A 109(28):E1938–E1946
Aiken JM, Williamson JL et al (1990) Presence of mitochondrial D-loop DNA in scrapie-infected brain preparations enriched for the prion protein. J Virol 64(7):3265–3268
Klein TR, Kirsch D et al (1998) Prion rods contain small amounts of two host sphingolipids as revealed by thin-layer chromatography and mass spectrometry. Biol Chem 379(6):655–666
Snow AD, Kisilevsky R et al (1989) Sulfated glycosaminoglycans in amyloid plaques of prion diseases. Acta Neuropathol 77(4):337–342
Wang F, Wang X et al (2010) Generating a prion with bacterially expressed recombinant prion protein. Science 327(5969):1132–1135
Barron RM, Campbell SL et al (2007) High titers of transmissible spongiform encephalopathy infectivity associated with extremely low levels of PrPSc in vivo. J Biol Chem 282(49):35878–35886
Coleman BM, Harrison CF et al (2014) Pathogenic mutations within the hydrophobic domain of the prion protein lead to the formation of protease-sensitive prion species with increased lethality. J Virol 88(5):2690–2703
Lewis V, Haigh CL et al (2012) Prion subcellular fractionation reveals infectivity spectrum, with a high titre-low PrPres level disparity. Mol Neurodegener 7:18
Gambetti P, Dong Z et al (2008) A novel human disease with abnormal prion protein sensitive to protease. Ann Neurol 63(6):697–708
Diack AB, Ritchie DL et al (2014) Variably protease-sensitive prionopathy, a unique prion variant with inefficient transmission properties. Emerg Infect Dis 20(12):1969–1979
Forloni G, Angeretti N et al (1993) Neurotoxicity of a prion protein fragment. Nature 362(6420):543–546
Salahuddin P, Fatima MT et al (2016) Structure of amyloid oligomers and their mechanisms of toxicities: targeting amyloid oligomers using novel therapeutic approaches. Eur J Med Chem 114:41–58
Weise J, Crome O et al (2004) Upregulation of cellular prion protein (PrPc) after focal cerebral ischemia and influence of lesion severity. Neurosci Lett 372(1–2):146–150
Sakurai-Yamashita Y, Sakaguchi S et al (2005) Female-specific neuroprotection against transient brain ischemia observed in mice devoid of prion protein is abolished by ectopic expression of prion protein-like protein. Neuroscience 136(1):281–287
Shmerling D, Hegyi I et al (1998) Expression of amino-terminally truncated PrP in the mouse leading to ataxia and specific cerebellar lesions. Cell 93(2):203–214
Donne DG, Viles JH et al (1997) Structure of the recombinant full-length hamster prion protein PrP(29-231): the N terminus is highly flexible. Proc Natl Acad Sci U S A 94(25):13452–13457
Riek R, Hornemann S et al (1997) NMR characterization of the full-length recombinant murine prion protein, mPrP(23-231). FEBS Lett 413(2):282–288
Solforosi L, Criado JR et al (2004) Cross-linking cellular prion protein triggers neuronal apoptosis in vivo. Science 303(5663):1514–1516
Sonati T, Reimann RR et al (2013) The toxicity of antiprion antibodies is mediated by the flexible tail of the prion protein. Nature 501(7465):102–106
Herrmann US, Sonati T et al (2015) Prion infections and anti-PrP antibodies trigger converging neurotoxic pathways. PLoS Pathog 11(2):e1004662
Lauren J, Gimbel DA et al (2009) Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature 457(7233):1128–1132
Klyubin I, Nicoll AJ et al (2014) Peripheral administration of a humanized anti-PrP antibody blocks Alzheimer’s disease Abeta synaptotoxicity. J Neurosci 34(18):6140–6145
Balducci C, Beeg M et al (2010) Synthetic amyloid-beta oligomers impair long-term memory independently of cellular prion protein. Proc Natl Acad Sci U S A 107(5):2295–2300
Calella AM, Farinelli M et al (2010) Prion protein and Abeta-related synaptic toxicity impairment. EMBO Mol Med 2(8):306–314
Cisse M, Sanchez PE et al (2011) 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 31(29):10427–10431
Kessels HW, Nguyen LN et al (2010) The prion protein as a receptor for amyloid-beta. Nature 466(7308):E3–E4. discussion E-5
Hegde RS, Mastrianni JA et al (1998) A transmembrane form of the prion protein in neurodegenerative disease. Science 279(5352):827–834
Hegde RS, Tremblay P et al (1999) Transmissible and genetic prion diseases share a common pathway of neurodegeneration. Nature 402(6763):822–826
Drisaldi B, Stewart RS et al (2003) Mutant PrP is delayed in its exit from the endoplasmic reticulum, but neither wild-type nor mutant PrP undergoes retrotranslocation prior to proteasomal degradation. J Biol Chem 278(24):21732–21743
Stewart RS, Drisaldi B et al (2001) A transmembrane form of the prion protein contains an uncleaved signal peptide and is retained in the endoplasmic reticulum. Mol Biol Cell 12(4):881–889
Stewart RS, Piccardo P et al (2005) Neurodegenerative illness in transgenic mice expressing a transmembrane form of the prion protein. J Neurosci 25(13):3469–3477
Rane NS, Yonkovich JL et al (2004) Protection from cytosolic prion protein toxicity by modulation of protein translocation. EMBO J 23(23):4550–4559
Ma J, Lindquist S (2001) Wild-type PrP and a mutant associated with prion disease are subject to retrograde transport and proteasome degradation. Proc Natl Acad Sci U S A 98(26):14955–14960
Ma J, Lindquist S (2002) Conversion of PrP to a self-perpetuating PrPSc-like conformation in the cytosol. Science 298(5599):1785–1788
Ma J, Wollmann R et al (2002) Neurotoxicity and neurodegeneration when PrP accumulates in the cytosol. Science 298(5599):1781–1785
Yedidia Y, Horonchik L et al (2001) Proteasomes and ubiquitin are involved in the turnover of the wild-type prion protein. EMBO J 20(19):5383–5391
Hetz C, Russelakis-Carneiro M et al (2003) Caspase-12 and endoplasmic reticulum stress mediate neurotoxicity of pathological prion protein. EMBO J 22(20):5435–5445
Bertolotti A, Zhang Y et al (2000) Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat Cell Biol 2(6):326–332
Shen J, Snapp EL et al (2005) Stable binding of ATF6 to BiP in the endoplasmic reticulum stress response. Mol Cell Biol 25(3):921–932
Ferreiro E, Resende R et al (2006) An endoplasmic-reticulum-specific apoptotic pathway is involved in prion and amyloid-beta peptides neurotoxicity. Neurobiol Dis 23(3):669–678
Moreno JA, Halliday M et al (2013) Oral treatment targeting the unfolded protein response prevents neurodegeneration and clinical disease in prion-infected mice. Sci Transl Med 5(206):206ra138
Budka H, Aguzzi A et al (1995) Neuropathological diagnostic criteria for Creutzfeldt-Jakob disease (CJD) and other human spongiform encephalopathies (prion diseases). Brain Pathol 5(4):459–466
Jeffrey M, Gonzalez L (2007) Classical sheep transmissible spongiform encephalopathies: pathogenesis, pathological phenotypes and clinical disease. Neuropathol Appl Neurobiol 33(4):373–394
Carroll JA, Striebel JF et al (2015) Prion infection of mouse brain reveals multiple new upregulated genes involved in neuroinflammation or signal transduction. J Virol 89(4):2388–2404
Carroll JA, Striebel JF et al (2016) Prion strain differences in accumulation of PrPSc on neurons and glia are associated with similar expression profiles of neuroinflammatory genes: comparison of three prion strains. PLoS Pathog 12(4):e1005551
Felton LM, Cunningham C et al (2005) MCP-1 and murine prion disease: separation of early behavioural dysfunction from overt clinical disease. Neurobiol Dis 20(2):283–295
Tamguney G, Giles K et al (2008) Genes contributing to prion pathogenesis. J Gen Virol 89(Pt 7):1777–1788
Tribouillard-Tanvier D, Race B et al (2012) Early cytokine elevation, PrPres deposition, and gliosis in mouse scrapie: no effect on disease by deletion of cytokine genes IL-12p40 and IL-12p35. J Virol 86(19):10377–10383
Brandner S, Isenmann S et al (1996) Normal host prion protein necessary for scrapie-induced neurotoxicity. Nature 379(6563):339–343
White MD, Farmer M et al (2008) Single treatment with RNAi against prion protein rescues early neuronal dysfunction and prolongs survival in mice with prion disease. Proc Natl Acad Sci U S A 105(29):10238–10243
Mallucci G, Dickinson A et al (2003) Depleting neuronal PrP in prion infection prevents disease and reverses spongiosis. Science 302(5646):871–874
Jeffrey M, Goodsir CM et al (2004) Scrapie-specific neuronal lesions are independent of neuronal PrP expression. Ann Neurol 55(6):781–792
Chesebro B, Trifilo M et al (2005) Anchorless prion protein results in infectious amyloid disease without clinical scrapie. Science 308(5727):1435–1439
Chesebro B, Race B et al (2010) Fatal transmissible amyloid encephalopathy: a new type of prion disease associated with lack of prion protein membrane anchoring. PLoS Pathog 6(3):e1000800
Koperek O, Kovacs GG et al (2002) Disease-associated prion protein in vessel walls. Am J Pathol 161(6):1979–1984
Haigh CL, Lawson VA et al (2014) Blood vessel cell death during prion disease: implications for disease management and infection control. Exp Hematol 42(11):939–940
Collinge J, Clarke AR (2007) A general model of prion strains and their pathogenicity. Science 318(5852):930–936
Simoneau S, Rezaei H et al (2007) In vitro and in vivo neurotoxicity of prion protein oligomers. PLoS Pathog 3(8):e125
Zhou M, Ottenberg G et al (2012) Highly neurotoxic monomeric alpha-helical prion protein. Proc Natl Acad Sci U S A 109(8):3113–3118
Collins SJ, Sanchez-Juan P et al (2006) Determinants of diagnostic investigation sensitivities across the clinical spectrum of sporadic Creutzfeldt-Jakob disease. Brain 129(Pt 9):2278–2287
Schmitz M, Ebert E et al (2016) Validation of 14-3-3 protein as a marker in sporadic Creutzfeldt-Jakob Disease diagnostic. Mol Neurobiol 53(4):2189–2199
Soto C, Anderes L et al (2005) Pre-symptomatic detection of prions by cyclic amplification of protein misfolding. FEBS Lett 579(3):638–642
Atarashi R, Moore RA et al (2007) Ultrasensitive detection of scrapie prion protein using seeded conversion of recombinant prion protein. Nat Methods 4(8):645–650
Doh-Ura K, Iwaki T et al (2000) Lysosomotropic agents and cysteine protease inhibitors inhibit scrapie-associated prion protein accumulation. J Virol 74(10):4894–4897
Korth C, May BC et al (2001) Acridine and phenothiazine derivatives as pharmacotherapeutics for prion disease. Proc Natl Acad Sci U S A 98(17):9836–9841
Caughey B, Raymond GJ (1993) Sulfated polyanion inhibition of scrapie-associated PrP accumulation in cultured cells. J Virol 67(2):643–650
Doh-ura K, Ishikawa K et al (2004) Treatment of transmissible spongiform encephalopathy by intraventricular drug infusion in animal models. J Virol 78(10):4999–5006
Perovic S, Bohm M et al (1998) Pharmacological intervention in age-associated brain disorders by Flupirtine: Alzheimer's and prion diseases. Mech Ageing Dev 101(1–2):1–19
Mange A, Milhavet O et al (2000) Effect of amphotericin B on wild-type and mutated prion proteins in cultured cells: putative mechanism of action in transmissible spongiform encephalopathies. J Neurochem 74(2):754–762
Forloni G, Iussich S et al (2002) Tetracyclines affect prion infectivity. Proc Natl Acad Sci U S A 99(16):10849–10854
Tagliavini F, Forloni G et al (2000) Tetracycline affects abnormal properties of synthetic PrP peptides and PrP(Sc) in vitro. J Mol Biol 300(5):1309–1322
Otto M, Cepek L et al (2004) Efficacy of flupirtine on cognitive function in patients with CJD: a double-blind study. Neurology 62(5):714–718
Geschwind MD, Kuo AL et al (2013) Quinacrine treatment trial for sporadic Creutzfeldt-Jakob disease. Neurology 81(23):2015–2023
Bone I, Belton L et al (2008) Intraventricular pentosan polysulphate in human prion diseases: an observational study in the UK. Eur J Neurol 15(5):458–464
Tsuboi Y, Doh-Ura K et al (2009) Continuous intraventricular infusion of pentosan polysulfate: clinical trial against prion diseases. Neuropathology 29(5):632–636
Haik S, Marcon G et al (2014) Doxycycline in Creutzfeldt-Jakob disease: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Neurol 13(2):150–158
Kim MO, Geschwind MD (2015) Clinical update of Jakob-Creutzfeldt disease. Curr Opin Neurol 28(3):302–310
Lawson VA, Vella LJ et al (2008) Mouse-adapted sporadic human Creutzfeldt-Jakob disease prions propagate in cell culture. Int J Biochem Cell Biol 40(12):2793–2801
Priola SA, Chesebro B (1995) A single hamster PrP amino acid blocks conversion to protease-resistant PrP in scrapie-infected mouse neuroblastoma cells. J Virol 69(12):7754–7758
Priola SA, Lawson VA (2001) Glycosylation influences cross-species formation of protease-resistant prion protein. EMBO J 20(23):6692–6699
Torres JM, Espinosa JC et al (2014) Elements modulating the prion species barrier and its passage consequences. PLoS One 9(3):e89722
Wiseman FK, Cancellotti E et al (2015) The glycosylation status of PrPC is a key factor in determining transmissible spongiform encephalopathy transmission between species. J Virol 89(9):4738–4747
Caughey B, Raymond GJ et al (1998) Strain-dependent differences in beta-sheet conformations of abnormal prion protein. J Biol Chem 273(48):32230–32235
Hill AF, Joiner S et al (2003) Molecular classification of sporadic Creutzfeldt-Jakob disease. Brain 126(Pt 6):1333–1346
Klemm HM, Welton JM et al (2012) The prion protein preference of sporadic Creutzfeldt-Jakob disease subtypes. J Biol Chem 287(43):36465–36472
Kim C, Haldiman T et al (2012) Small protease sensitive oligomers of PrPSc in distinct human prions determine conversion rate of PrP(C). PLoS Pathog 8(8):e1002835
Collinge J, Sidle KC et al (1996) Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD. Nature 383(6602):685–690
Lewis V, Hill AF et al (2005) Australian sporadic CJD analysis supports endogenous determinants of molecular-clinical profiles. Neurology 65(1):113–118
Parchi P, Castellani R et al (1996) Molecular basis of phenotypic variability in sporadic Creutzfeldt-Jakob disease. Ann Neurol 39(6):767–778
Peden AH, Head MW et al (2004) Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 364(9433):527–529
Lee HS, Brown P et al (2001) Increased susceptibility to Kuru of carriers of the PRNP 129 methionine/methionine genotype. J Infect Dis 183(2):192–196
Cervenakova L, Goldfarb LG et al (1998) Phenotype-genotype studies in kuru: implications for new variant Creutzfeldt-Jakob disease. Proc Natl Acad Sci U S A 95(22):13239–13241
Gill ON, Spencer Y et al (2013) Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey. BMJ 347:f5675
Hilton DA, Ghani AC et al (2004) Prevalence of lymphoreticular prion protein accumulation in UK tissue samples. J Pathol 203(3):733–739
Ironside JW, Bishop MT et al (2006) Variant Creutzfeldt-Jakob disease: prion protein genotype analysis of positive appendix tissue samples from a retrospective prevalence study. BMJ 332(7551):1186–1188
Asante EA, Smidak M et al (2015) A naturally occurring variant of the human prion protein completely prevents prion disease. Nature 522(7557):478–481
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Whitechurch, B.C., Welton, J.M., Collins, S.J., Lawson, V.A. (2017). Prion Diseases. In: Beart, P., Robinson, M., Rattray, M., Maragakis, N. (eds) Neurodegenerative Diseases. Advances in Neurobiology, vol 15. Springer, Cham. https://doi.org/10.1007/978-3-319-57193-5_13
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