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Review article: Biomedical intelligence

Vol. 147 No. 1516 (2017)

Prions, prionoid complexes and amyloids: the bad, the good and something in between

Cite this as:
Swiss Med Wkly. 2017;147:w14424


Prions are infectious agents causing transmissible spongiform encephalopathies in humans and animals. These protein-based particles template conformational changes in a host-encoded prion protein to an insoluble self-like conformation. Prions are also present in yeast, where they support protein-based epigenetic inheritance. There is emerging evidence that prion-like (prionoid) particles can support a variety of pathological and beneficial functions. The recent data on the prionoid spread of other pathological amyloids are discussed in light of differences between prions and prion-like aggregates. On the other hand, prion-like action has also been found to support important functions such as memory, and amyloids were shown to have a variety of physiological roles from storage to scaffolding in simple organisms and in humans. Higher-order protein complexes play important roles in signalling. Many death-fold domains can polymerise upon nucleation to enhance sensitivity and induce a robust response. Although these polymers are structurally different from amyloids, some of them are characterised by prionoid activities, such as intercellular spread. The initial activation of these complexes is vital for organismal health, whereas prolonged activation leading to unresolved inflammation underlies autoinflammatory and other diseases. Prionoid complexes play important roles far beyond prion diseases and neurodegeneration.


  1. Chiti F, Dobson CM. Protein misfolding, functional amyloid, and human disease. Annu Rev Biochem. 2006;75(1):333–66.
  2. Sipe JD, Benson MD, Buxbaum JN, Ikeda S, Merlini G, Saraiva MJ, et al.; Nomenclature Committee of the International Society of Amyloidosis. Amyloid fibril protein nomenclature: 2012 recommendations from the Nomenclature Committee of the International Society of Amyloidosis. Amyloid. 2012;19(4):167–70.
  3. Eisenberg D, Jucker M. The amyloid state of proteins in human diseases. Cell. 2012;148(6):1188–203.
  4. Chiti F, Webster P, Taddei N, Clark A, Stefani M, Ramponi G, et al. Designing conditions for in vitro formation of amyloid protofilaments and fibrils. Proc Natl Acad Sci USA. 1999;96(7):3590–4.
  5. Xiao Y, Ma B, McElheny D, Parthasarathy S, Long F, Hoshi M, et al. Aβ(1-42) fibril structure illuminates self-recognition and replication of amyloid in Alzheimer’s disease. Nat Struct Mol Biol. 2015;22(6):499–505.
  6. Van Melckebeke H, Wasmer C, Lange A, Ab E, Loquet A, Böckmann A, et al. Atomic-resolution three-dimensional structure of HET-s(218-289) amyloid fibrils by solid-state NMR spectroscopy. J Am Chem Soc. 2010;132(39):13765–75.
  7. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, et al. UCSF Chimera--a visualization system for exploratory research and analysis. J Comput Chem. 2004;25(13):1605–12.
  8. Sunde M, Serpell LC, Bartlam M, Fraser PE, Pepys MB, Blake CC. Common core structure of amyloid fibrils by synchrotron X-ray diffraction. J Mol Biol. 1997;273(3):729–39.
  9. Benzinger TL, Gregory DM, Burkoth TS, Miller-Auer H, Lynn DG, Botto RE, et al. Propagating structure of Alzheimer’s beta-amyloid(10-35) is parallel beta-sheet with residues in exact register. Proc Natl Acad Sci USA. 1998;95(23):13407–12.
  10. Tycko R. Solid-state NMR studies of amyloid fibril structure. Annu Rev Phys Chem. 2011;62(1):279–99.
  11. Makin OS, Atkins E, Sikorski P, Johansson J, Serpell LC. Molecular basis for amyloid fibril formation and stability. Proc Natl Acad Sci USA. 2005;102(2):315–20.
  12. Nelson R, Sawaya MR, Balbirnie M, Madsen AO, Riekel C, Grothe R, et al. Structure of the cross-beta spine of amyloid-like fibrils. Nature. 2005;435(7043):773–8.
  13. Sawaya MR, Sambashivan S, Nelson R, Ivanova MI, Sievers SA, Apostol MI, et al. Atomic structures of amyloid cross-beta spines reveal varied steric zippers. Nature. 2007;447(7143):453–7.
  14. Wu H, Fuxreiter M. The Structure and Dynamics of Higher-Order Assemblies: Amyloids, Signalosomes, and Granules. Cell. 2016;165(5):1055–66.
  15. Knowles TP, Waudby CA, Devlin GL, Cohen SI, Aguzzi A, Vendruscolo M, et al. An analytical solution to the kinetics of breakable filament assembly. Science. 2009;326(5959):1533–7.
  16. Arosio P, Knowles TP, Linse S. On the lag phase in amyloid fibril formation. Phys Chem Chem Phys. 2015;17(12):7606–18.
  17. Prusiner SB. Novel proteinaceous infectious particles cause scrapie. Science. 1982;216(4542):136–44.
  18. Wang F, Wang X, Yuan CG, Ma J. Generating a prion with bacterially expressed recombinant prion protein. Science. 2010;327(5969):1132–5.
  19. Baker HF, Ridley RM, Duchen LW, Crow TJ, Bruton CJ. Experimental induction of beta-amyloid plaques and cerebral angiopathy in primates. Ann N Y Acad Sci. 1993;695(1):228–31.
  20. Baker HF, Ridley RM, Duchen LW, Crow TJ, Bruton CJ. Induction of beta (A4)-amyloid in primates by injection of Alzheimer’s disease brain homogenate. Comparison with transmission of spongiform encephalopathy. Mol Neurobiol. 1994;8(1):25–39.
  21. Baker HF, Ridley RM, Wells GA. Experimental transmission of BSE and scrapie to the common marmoset. Vet Rec. 1993;132(16):403–6.
  22. Eisele YS, Bolmont T, Heikenwalder M, Langer F, Jacobson LH, Yan ZX, et al. Induction of cerebral beta-amyloidosis: intracerebral versus systemic Abeta inoculation. Proc Natl Acad Sci USA. 2009;106(31):12926–31.
  23. Eisele YS, Obermüller U, Heilbronner G, Baumann F, Kaeser SA, Wolburg H, et al. Peripherally applied Abeta-containing inoculates induce cerebral beta-amyloidosis. Science. 2010;330(6006):980–2.
  24. Langer F, Eisele YS, Fritschi SK, Staufenbiel M, Walker LC, Jucker M. Soluble Aβ seeds are potent inducers of cerebral β-amyloid deposition. J Neurosci. 2011;31(41):14488–95.
  25. Meyer-Luehmann M, Coomaraswamy J, Bolmont T, Kaeser S, Schaefer C, Kilger E, et al. Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and host. Science. 2006;313(5794):1781–4.
  26. Watts JC, Condello C, Stöhr J, Oehler A, Lee J, DeArmond SJ, et al. Serial propagation of distinct strains of Aβ prions from Alzheimer’s disease patients. Proc Natl Acad Sci USA. 2014;111(28):10323–8.
  27. Stöhr J, Condello C, Watts JC, Bloch L, Oehler A, Nick M, et al. Distinct synthetic Aβ prion strains producing different amyloid deposits in bigenic mice. Proc Natl Acad Sci USA. 2014;111(28):10329–34.
  28. Iba M, Guo JL, McBride JD, Zhang B, Trojanowski JQ, Lee VM. Synthetic tau fibrils mediate transmission of neurofibrillary tangles in a transgenic mouse model of Alzheimer’s-like tauopathy. J Neurosci. 2013;33(3):1024–37.
  29. Clavaguera F, Bolmont T, Crowther RA, Abramowski D, Frank S, Probst A, et al. Transmission and spreading of tauopathy in transgenic mouse brain. Nat Cell Biol. 2009;11(7):909–13.
  30. Peeraer E, Bottelbergs A, Van Kolen K, Stancu IC, Vasconcelos B, Mahieu M, et al. Intracerebral injection of preformed synthetic tau fibrils initiates widespread tauopathy and neuronal loss in the brains of tau transgenic mice. Neurobiol Dis. 2015;73:83–95.
  31. Sanders DW, Kaufman SK, DeVos SL, Sharma AM, Mirbaha H, Li A, et al. Distinct tau prion strains propagate in cells and mice and define different tauopathies. Neuron. 2014;82(6):1271–88.
  32. Luk KC, Kehm VM, Zhang B, O’Brien P, Trojanowski JQ, Lee VM. Intracerebral inoculation of pathological α-synuclein initiates a rapidly progressive neurodegenerative α-synucleinopathy in mice. J Exp Med. 2012;209(5):975–86.
  33. Masuda-Suzukake M, Nonaka T, Hosokawa M, Oikawa T, Arai T, Akiyama H, et al. Prion-like spreading of pathological α-synuclein in brain. Brain. 2013;136(Pt 4):1128–38.
  34. Sacino AN, Brooks M, McGarvey NH, McKinney AB, Thomas MA, Levites Y, et al. Induction of CNS α-synuclein pathology by fibrillar and non-amyloidogenic recombinant α-synuclein. Acta Neuropathol Commun. 2013;1(1):38.
  35. Jones DR, Delenclos M, Baine AT, DeTure M, Murray ME, Dickson DW, et al. Transmission of Soluble and Insoluble α-Synuclein to Mice. J Neuropathol Exp Neurol. 2015;74(12):1158–69.
  36. Prusiner SB, Woerman AL, Mordes DA, Watts JC, Rampersaud R, Berry DB, et al. Evidence for α-synuclein prions causing multiple system atrophy in humans with parkinsonism. Proc Natl Acad Sci USA. 2015;112(38):E5308–17.
  37. Lundmark K, Westermark GT, Nyström S, Murphy CL, Solomon A, Westermark P. Transmissibility of systemic amyloidosis by a prion-like mechanism. Proc Natl Acad Sci USA. 2002;99(10):6979–84. Erratum in: Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3543.
  38. Solomon A, Richey T, Murphy CL, Weiss DT, Wall JS, Westermark GT, et al. Amyloidogenic potential of foie gras. Proc Natl Acad Sci USA. 2007;104(26):10998–1001.
  39. Zhang B, Une Y, Fu X, Yan J, Ge F, Yao J, et al. Fecal transmission of AA amyloidosis in the cheetah contributes to high incidence of disease. Proc Natl Acad Sci USA. 2008;105(20):7263–8.
  40. Si K, Giustetto M, Etkin A, Hsu R, Janisiewicz AM, Miniaci MC, et al. A neuronal isoform of CPEB regulates local protein synthesis and stabilizes synapse-specific long-term facilitation in aplysia. Cell. 2003;115(7):893–904.
  41. Si K, Lindquist S, Kandel ER. A neuronal isoform of the aplysia CPEB has prion-like properties. Cell. 2003;115(7):879–91.
  42. Si K, Choi YB, White-Grindley E, Majumdar A, Kandel ER. Aplysia CPEB can form prion-like multimers in sensory neurons that contribute to long-term facilitation. Cell. 2010;140(3):421–35.
  43. Keleman K, Krüttner S, Alenius M, Dickson BJ. Function of the Drosophila CPEB protein Orb2 in long-term courtship memory. Nat Neurosci. 2007;10(12):1587–93.
  44. Majumdar A, Cesario WC, White-Grindley E, Jiang H, Ren F, Khan MR, et al. Critical role of amyloid-like oligomers of Drosophila Orb2 in the persistence of memory. Cell. 2012;148(3):515–29.
  45. Fioriti L, Myers C, Huang YY, Li X, Stephan JS, Trifilieff P, et al. The Persistence of Hippocampal-Based Memory Requires Protein Synthesis Mediated by the Prion-like Protein CPEB3. Neuron. 2015;86(6):1433–48.
  46. Stephan JS, Fioriti L, Lamba N, Colnaghi L, Karl K, Derkatch IL, et al. The CPEB3 Protein Is a Functional Prion that Interacts with the Actin Cytoskeleton. Cell Reports. 2015;11(11):1772–85.
  47. Drisaldi B, Colnaghi L, Fioriti L, Rao N, Myers C, Snyder AM, et al. SUMOylation Is an Inhibitory Constraint that Regulates the Prion-like Aggregation and Activity of CPEB3. Cell Reports. 2015;11(11):1694–702.
  48. Chakrabortee S, Kayatekin C, Newby GA, Mendillo ML, Lancaster A, Lindquist S. Luminidependens (LD) is an Arabidopsis protein with prion behavior. Proc Natl Acad Sci USA. 2016;113(21):6065–70.
  49. Chapman MR, Robinson LS, Pinkner JS, Roth R, Heuser J, Hammar M, et al. Role of Escherichia coli curli operons in directing amyloid fiber formation. Science. 2002;295(5556):851–5.
  50. Barnhart MM, Chapman MR. Curli biogenesis and function. Annu Rev Microbiol. 2006;60(1):131–47.
  51. Hammer ND, Schmidt JC, Chapman MR. The curli nucleator protein, CsgB, contains an amyloidogenic domain that directs CsgA polymerization. Proc Natl Acad Sci USA. 2007;104(30):12494–9.
  52. Robinson LS, Ashman EM, Hultgren SJ, Chapman MR. Secretion of curli fibre subunits is mediated by the outer membrane-localized CsgG protein. Mol Microbiol. 2006;59(3):870–81.
  53. Nenninger AA, Robinson LS, Hultgren SJ. Localized and efficient curli nucleation requires the chaperone-like amyloid assembly protein CsgF. Proc Natl Acad Sci USA. 2009;106(3):900–5.
  54. Nenninger AA, Robinson LS, Hammer ND, Epstein EA, Badtke MP, Hultgren SJ, et al. CsgE is a curli secretion specificity factor that prevents amyloid fibre aggregation. Mol Microbiol. 2011;81(2):486–99.
  55. Zhou Y, Smith D, Leong BJ, Brännström K, Almqvist F, Chapman MR. Promiscuous cross-seeding between bacterial amyloids promotes interspecies biofilms. J Biol Chem. 2012;287(42):35092–103.
  56. Branda SS, Chu F, Kearns DB, Losick R, Kolter R. A major protein component of the Bacillus subtilis biofilm matrix. Mol Microbiol. 2006;59(4):1229–38.
  57. Romero D, Aguilar C, Losick R, Kolter R. Amyloid fibers provide structural integrity to Bacillus subtilis biofilms. Proc Natl Acad Sci USA. 2010;107(5):2230–4.
  58. Romero D, Vlamakis H, Losick R, Kolter R. An accessory protein required for anchoring and assembly of amyloid fibres in B. subtilis biofilms. Mol Microbiol. 2011;80(5):1155–68.
  59. Stöver AG, Driks A. Secretion, localization, and antibacterial activity of TasA, a Bacillus subtilis spore-associated protein. J Bacteriol. 1999;181(5):1664–72.
  60. Kearns DB, Chu F, Branda SS, Kolter R, Losick R. A master regulator for biofilm formation by Bacillus subtilis. Mol Microbiol. 2005;55(3):739–49.
  61. Iconomidou VA, Vriend G, Hamodrakas SJ. Amyloids protect the silkmoth oocyte and embryo. FEBS Lett. 2000;479(3):141–5.
  62. Hamodrakas SJ, Hoenger A, Iconomidou VA. Amyloid fibrillogenesis of silkmoth chorion protein peptide-analogues via a liquid-crystalline intermediate phase. J Struct Biol. 2004;145(3):226–35.
  63. Kenney JM, Knight D, Wise MJ, Vollrath F. Amyloidogenic nature of spider silk. Eur J Biochem. 2002;269(16):4159–63.
  64. Knight DP, Knight MM, Vollrath F. Beta transition and stress-induced phase separation in the spinning of spider dragline silk. Int J Biol Macromol. 2000;27(3):205–10.
  65. Vollrath F, Knight DP. Liquid crystalline spinning of spider silk. Nature. 2001;410(6828):541–8.
  66. Maji SK, Perrin MH, Sawaya MR, Jessberger S, Vadodaria K, Rissman RA, et al. Functional amyloids as natural storage of peptide hormones in pituitary secretory granules. Science. 2009;325(5938):328–32.
  67. Boke E, Ruer M, Wühr M, Coughlin M, Lemaitre R, Gygi SP, et al. Amyloid-like Self-Assembly of a Cellular Compartment. Cell. 2016;166(3):637–50.
  68. Giraldo R. Defined DNA sequences promote the assembly of a bacterial protein into distinct amyloid nanostructures. Proc Natl Acad Sci USA. 2007;104(44):17388–93.
  69. Fernández-Tresguerres ME, de la Espina SM, Gasset-Rosa F, Giraldo R. A DNA-promoted amyloid proteinopathy in Escherichia coli. Mol Microbiol. 2010;77(6):1456–69.
  70. Gasset-Rosa F, Coquel AS, Moreno-Del Álamo M, Chen P, Song X, Serrano AM, et al. Direct assessment in bacteria of prionoid propagation and phenotype selection by Hsp70 chaperone. Mol Microbiol. 2014;91(6):1070–87.
  71. Molina-García L, Gasset-Rosa F, Moreno-Del Álamo M, Fernández-Tresguerres ME, Moreno-Díaz de la Espina S, Lurz R, et al. Functional amyloids as inhibitors of plasmid DNA replication. Sci Rep. 2016;6:25425.
  72. Fowler DM, Koulov AV, Alory-Jost C, Marks MS, Balch WE, Kelly JW. Functional amyloid formation within mammalian tissue. PLoS Biol. 2005;4(1):e6.
  73. Wickner RB. [URE3] as an altered URE2 protein: evidence for a prion analog in Saccharomyces cerevisiae. Science. 1994;264(5158):566–9.
  74. Patino MM, Liu JJ, Glover JR, Lindquist S. Support for the prion hypothesis for inheritance of a phenotypic trait in yeast. Science. 1996;273(5275):622–6.
  75. Paushkin SV, Kushnirov VV, Smirnov VN, Ter-Avanesyan MD. In vitro propagation of the prion-like state of yeast Sup35 protein. Science. 1997;277(5324):381–3.
  76. Sparrer HE, Santoso A, Szoka FC, Jr, Weissman JS. Evidence for the prion hypothesis: induction of the yeast [PSI+] factor by in vitro- converted Sup35 protein. Science. 2000;289(5479):595–9.
  77. Bradley ME, Edskes HK, Hong JY, Wickner RB, Liebman SW. Interactions among prions and prion “strains” in yeast. Proc Natl Acad Sci USA. 2002;99(Suppl 4):16392–9.
  78. Tanaka M, Collins SR, Toyama BH, Weissman JS. The physical basis of how prion conformations determine strain phenotypes. Nature. 2006;442(7102):585–9.
  79. Cai X, Chen J, Xu H, Liu S, Jiang QX, Halfmann R, et al. Prion-like polymerization underlies signal transduction in antiviral immune defense and inflammasome activation. Cell. 2014;156(6):1207–22.
  80. Hou F, Sun L, Zheng H, Skaug B, Jiang QX, Chen ZJ. MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response. Cell. 2011;146(3):448–61.
  81. Seth RB, Sun L, Ea CK, Chen ZJ. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell. 2005;122(5):669–82.
  82. Tang ED, Wang CY. MAVS self-association mediates antiviral innate immune signaling. J Virol. 2009;83(8):3420–8.
  83. Xu H, He X, Zheng H, Huang LJ, Hou F, Yu Z, et al. Structural basis for the prion-like MAVS filaments in antiviral innate immunity. eLife. 2014;3:e01489.
  84. Hu Z, Zhou Q, Zhang C, Fan S, Cheng W, Zhao Y, et al. Structural and biochemical basis for induced self-propagation of NLRC4. Science. 2015;350(6259):399–404.
  85. Zhang L, Chen S, Ruan J, Wu J, Tong AB, Yin Q, et al. Cryo-EM structure of the activated NAIP2-NLRC4 inflammasome reveals nucleated polymerization. Science. 2015;350(6259):404–9.
  86. Diebolder CA, Halff EF, Koster AJ, Huizinga EG, Koning RI. Cryoelectron Tomography of the NAIP5/NLRC4 Inflammasome: Implications for NLR Activation. Structure. 2015;23(12):2349–57.
  87. Lu A, Magupalli VG, Ruan J, Yin Q, Atianand MK, Vos MR, et al. Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes. Cell. 2014;156(6):1193–206.
  88. Baroja-Mazo A, Martín-Sánchez F, Gomez AI, Martínez CM, Amores-Iniesta J, Compan V, et al. The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response. Nat Immunol. 2014;15(8):738–48.
  89. Franklin BS, Bossaller L, De Nardo D, Ratter JM, Stutz A, Engels G, et al. The adaptor ASC has extracellular and ‘prionoid’ activities that propagate inflammation. Nat Immunol. 2014;15(8):727–37.
  90. Li J, McQuade T, Siemer AB, Napetschnig J, Moriwaki K, Hsiao YS, et al. The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis. Cell. 2012;150(2):339–50.
  91. Aguzzi A, Polymenidou M. Mammalian prion biology: one century of evolving concepts. Cell. 2004;116(2):313–27.
  92. Prusiner SB. Prions. Proc Natl Acad Sci USA. 1998;95(23):13363–83.
  93. Aguzzi A, Calella AM. Prions: protein aggregation and infectious diseases. Physiol Rev. 2009;89(4):1105–52.
  94. Küffer A, Lakkaraju AK, Mogha A, Petersen SC, Airich K, Doucerain C, et al. The prion protein is an agonistic ligand of the G protein-coupled receptor Adgrg6. Nature. 2016;536(7617):464–8.
  95. Brown P, Brandel JP, Sato T, Nakamura Y, MacKenzie J, Will RG, et al. Iatrogenic Creutzfeldt-Jakob disease, final assessment. Emerg Infect Dis. 2012;18(6):901–7.
  96. Gajdusek DC, Gibbs CJ, Alpers M. Experimental transmission of a Kuru-like syndrome to chimpanzees. Nature. 1966;209(5025):794–6.
  97. Griffith JS. Self-replication and scrapie. Nature. 1967;215(5105):1043–4.
  98. Büeler H, Aguzzi A, Sailer A, Greiner RA, Autenried P, Aguet M, et al. Mice devoid of PrP are resistant to scrapie. Cell. 1993;73(7):1339–47.
  99. Collinge J. Prion diseases of humans and animals: their causes and molecular basis. Annu Rev Neurosci. 2001;24(1):519–50.
  100. Eraña H, Castilla J. The architecture of prions: how understanding would provide new therapeutic insights. Swiss Med Wkly. 2016;146:w14354.
  101. Caughey B, Raymond GJ, Bessen RA. Strain-dependent differences in beta-sheet conformations of abnormal prion protein. J Biol Chem. 1998;273(48):32230–5.
  102. Legname G, Baskakov IV, Nguyen HO, Riesner D, Cohen FE, DeArmond SJ, et al. Synthetic mammalian prions. Science. 2004;305(5684):673–6.
  103. Colby DW, Giles K, Legname G, Wille H, Baskakov IV, DeArmond SJ, et al. Design and construction of diverse mammalian prion strains. Proc Natl Acad Sci USA. 2009;106(48):20417–22.
  104. Makarava N, Kovacs GG, Bocharova O, Savtchenko R, Alexeeva I, Budka H, et al. Recombinant prion protein induces a new transmissible prion disease in wild-type animals. Acta Neuropathol. 2010;119(2):177–87.
  105. Saborio GP, Permanne B, Soto C. Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature. 2001;411(6839):810–3.
  106. Castilla J, Saá P, Hetz C, Soto C. In vitro generation of infectious scrapie prions. Cell. 2005;121(2):195–206.
  107. Atarashi R, Moore RA, Sim VL, Hughson AG, Dorward DW, Onwubiko HA, et al. Ultrasensitive detection of scrapie prion protein using seeded conversion of recombinant prion protein. Nat Methods. 2007;4(8):645–50.
  108. Zhang Z, Zhang Y, Wang F, Wang X, Xu Y, Yang H, et al. De novo generation of infectious prions with bacterially expressed recombinant prion protein. FASEB J. 2013;27(12):4768–75.
  109. Guo JL, Lee VM. Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases. Nat Med. 2014;20(2):130–8.
  110. Eraña H, Venegas V, Moreno J, Castilla J. Prion-like disorders and Transmissible Spongiform Encephalopathies: An overview of the mechanistic features that are shared by the various disease-related misfolded proteins. Biochem Biophys Res Commun. 2016;S0006-291X(16)31430-9. 10.1016/j.bbrc.2016.08.166
  111. Ashe KH, Aguzzi A. Prions, prionoids and pathogenic proteins in Alzheimer disease. Prion. 2013;7(1):55–9.
  112. Aguzzi A, Rajendran L. The transcellular spread of cytosolic amyloids, prions, and prionoids. Neuron. 2009;64(6):783–90.
  113. Chia R, Tattum MH, Jones S, Collinge J, Fisher EM, Jackson GS. Superoxide dismutase 1 and tgSOD1 mouse spinal cord seed fibrils, suggesting a propagative cell death mechanism in amyotrophic lateral sclerosis. PLoS One. 2010;5(5):e10627.
  114. Laferriere F, Polymenidou M. Advances and challenges in understanding the multifaceted pathogenesis of amyotrophic lateral sclerosis. Swiss Med Wkly. 2015;145:w14054.
  115. Nussbaum JM, Schilling S, Cynis H, Silva A, Swanson E, Wangsanut T, et al. Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid-β. Nature. 2012;485(7400):651–5.
  116. Jaunmuktane Z, Mead S, Ellis M, Wadsworth JD, Nicoll AJ, Kenny J, et al. Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy. Nature. 2015;525(7568):247–50.
  117. Frontzek K, Lutz MI, Aguzzi A, Kovacs GG, Budka H. Amyloid-β pathology and cerebral amyloid angiopathy are frequent in iatrogenic Creutzfeldt-Jakob disease after dural grafting. Swiss Med Wkly. 2016;146:w14287.
  118. Liebman SW, Chernoff YO. Prions in yeast. Genetics. 2012;191(4):1041–72.
  119. Wickner RB. Yeast and Fungal Prions. Cold Spring Harb Perspect Biol. 2016;8(9):a023531.
  120. Masison DC, Wickner RB. Prion-inducing domain of yeast Ure2p and protease resistance of Ure2p in prion-containing cells. Science. 1995;270(5233):93–5.
  121. Michelitsch MD, Weissman JS. A census of glutamine/asparagine-rich regions: implications for their conserved function and the prediction of novel prions. Proc Natl Acad Sci USA. 2000;97(22):11910–5.
  122. Sondheimer N, Lindquist S. Rnq1: an epigenetic modifier of protein function in yeast. Mol Cell. 2000;5(1):163–72.
  123. Tuite MF. Yeast prions and their prion-forming domain. Cell. 2000;100(3):289–92.
  124. Alberti S, Halfmann R, King O, Kapila A, Lindquist S. A systematic survey identifies prions and illuminates sequence features of prionogenic proteins. Cell. 2009;137(1):146–58.
  125. Wickner RB, Kelly AC. Prions are affected by evolution at two levels. Cell Mol Life Sci. 2016;73(6):1131–44.
  126. Krammer C, Kryndushkin D, Suhre MH, Kremmer E, Hofmann A, Pfeifer A, et al. The yeast Sup35NM domain propagates as a prion in mammalian cells. Proc Natl Acad Sci USA. 2009;106(2):462–7.
  127. Hofmann JP, Denner P, Nussbaum-Krammer C, Kuhn PH, Suhre MH, Scheibel T, et al. Cell-to-cell propagation of infectious cytosolic protein aggregates. Proc Natl Acad Sci USA. 2013;110(15):5951–6.
  128. de Moor CH, Richter JD. Cytoplasmic polyadenylation elements mediate masking and unmasking of cyclin B1 mRNA. EMBO J. 1999;18(8):2294–303.
  129. Miniaci MC, Kim JH, Puthanveettil SV, Si K, Zhu H, Kandel ER, et al. Sustained CPEB-dependent local protein synthesis is required to stabilize synaptic growth for persistence of long-term facilitation in Aplysia. Neuron. 2008;59(6):1024–36.
  130. Fiumara F, Rajasethupathy P, Antonov I, Kosmidis S, Sossin WS, Kandel ER. MicroRNA-22 Gates Long-Term Heterosynaptic Plasticity in Aplysia through Presynaptic Regulation of CPEB and Downstream Targets. Cell Reports. 2015;11(12):1866–75.
  131. White-Grindley E, Li L, Mohammad Khan R, Ren F, Saraf A, Florens L, et al. Contribution of Orb2A stability in regulated amyloid-like oligomerization of Drosophila Orb2. PLoS Biol. 2014;12(2):e1001786.
  132. Chao HW, Tsai LY, Lu YL, Lin PY, Huang WH, Chou HJ, et al. Deletion of CPEB3 enhances hippocampus-dependent memory via increasing expressions of PSD95 and NMDA receptors. J Neurosci. 2013;33(43):17008–22.
  133. Kinoshita T, Seki M. Epigenetic memory for stress response and adaptation in plants. Plant Cell Physiol. 2014;55(11):1859–63.
  134. Lancaster AK, Nutter-Upham A, Lindquist S, King OD. PLAAC: a web and command-line application to identify proteins with prion-like amino acid composition. Bioinformatics. 2014;30(17):2501–2.
  135. Blanco LP, Evans ML, Smith DR, Badtke MP, Chapman MR. Diversity, biogenesis and function of microbial amyloids. Trends Microbiol. 2012;20(2):66–73.
  136. Romero D, Kolter R. Functional amyloids in bacteria. Int Microbiol. 2014;17(2):65–73.
  137. Carrió M, González-Montalbán N, Vera A, Villaverde A, Ventura S. Amyloid-like properties of bacterial inclusion bodies. J Mol Biol. 2005;347(5):1025–37.
  138. Villaverde A. Bacterial inclusion bodies: an emerging platform for drug delivery and cell therapy. Nanomedicine (Lond). 2012;7(9):1277–9.
  139. Slotta U, Hess S, Spiess K, Stromer T, Serpell L, Scheibel T. Spider silk and amyloid fibrils: a structural comparison. Macromol Biosci. 2007;7(2):183–8.
  140. Monks JN, Yan B, Hawkins N, Vollrath F, Wang Z. Spider Silk: Mother Nature’s Bio-Superlens. Nano Lett. 2016;16(9):5842–5.
  141. Rising A, Johansson J. Toward spinning artificial spider silk. Nat Chem Biol. 2015;11(5):309–15.
  142. Tokareva O, Jacobsen M, Buehler M, Wong J, Kaplan DL. Structure-function-property-design interplay in biopolymers: spider silk. Acta Biomater. 2014;10(4):1612–26.
  143. Knowles TP, Mezzenga R. Amyloid Fibrils as Building Blocks for Natural and Artificial Functional Materials. Adv Mater. 2016;28(31):6546–61.
  144. Silveira JR, Raymond GJ, Hughson AG, Race RE, Sim VL, Hayes SF, et al. The most infectious prion protein particles. Nature. 2005;437(7056):257–61.
  145. Caughey B, Lansbury PT, Jr. Protofibrils, pores, fibrils, and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders. Annu Rev Neurosci. 2003;26(1):267–98.
  146. Richardson BE, Lehmann R. Mechanisms guiding primordial germ cell migration: strategies from different organisms. Nat Rev Mol Cell Biol. 2010;11(1):37–49.
  147. Dosch R, Wagner DS, Mintzer KA, Runke G, Wiemelt AP, Mullins MC. Maternal control of vertebrate development before the midblastula transition: mutants from the zebrafish I. Dev Cell. 2004;6(6):771–80.
  148. Marlow FL, Mullins MC. Bucky ball functions in Balbiani body assembly and animal-vegetal polarity in the oocyte and follicle cell layer in zebrafish. Dev Biol. 2008;321(1):40–50.
  149. Wu H. Higher-order assemblies in a new paradigm of signal transduction. Cell. 2013;153(2):287–92.
  150. Ferrao R, Wu H. Helical assembly in the death domain (DD) superfamily. Curr Opin Struct Biol. 2012;22(2):241–7.
  151. Zeng W, Sun L, Jiang X, Chen X, Hou F, Adhikari A, et al. Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity. Cell. 2010;141(2):315–30.
  152. Shi Y, Yuan B, Qi N, Zhu W, Su J, Li X, et al. An autoinhibitory mechanism modulates MAVS activity in antiviral innate immune response. Nat Commun. 2015;6:7811.
  153. Peisley A, Wu B, Yao H, Walz T, Hur S. RIG-I forms signaling-competent filaments in an ATP-dependent, ubiquitin-independent manner. Mol Cell. 2013;51(5):573–83.
  154. Peisley A, Wu B, Xu H, Chen ZJ, Hur S. Structural basis for ubiquitin-mediated antiviral signal activation by RIG-I. Nature. 2014;509(7498):110–4.
  155. Wu B, Peisley A, Tetrault D, Li Z, Egelman EH, Magor KE, et al. Molecular imprinting as a signal-activation mechanism of the viral RNA sensor RIG-I. Mol Cell. 2014;55(4):511–23.
  156. Dick MS, Sborgi L, Rühl S, Hiller S, Broz P. ASC filament formation serves as a signal amplification mechanism for inflammasomes. Nat Commun. 2016;7:11929.
  157. Wu B, Peisley A, Richards C, Yao H, Zeng X, Lin C, et al. Structural basis for dsRNA recognition, filament formation, and antiviral signal activation by MDA5. Cell. 2013;152(1-2):276–89.
  158. Gack MU, Shin YC, Joo CH, Urano T, Liang C, Sun L, et al. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature. 2007;446(7138):916–20.
  159. Wu B, Hur S. How RIG-I like receptors activate MAVS. Curr Opin Virol. 2015;12:91–8.
  160. Rutsch F, MacDougall M, Lu C, Buers I, Mamaeva O, Nitschke Y, et al. A specific IFIH1 gain-of-function mutation causes Singleton-Merten syndrome. Am J Hum Genet. 2015;96(2):275–82.
  161. Rice GI, del Toro Duany Y, Jenkinson EM, Forte GM, Anderson BH, Ariaudo G, et al. Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling. Nat Genet. 2014;46(5):503–9.
  162. Yoo YS, Park YY, Kim JH, Cho H, Kim SH, Lee HS, et al. The mitochondrial ubiquitin ligase MARCH5 resolves MAVS aggregates during antiviral signalling. Nat Commun. 2015;6:7910.
  163. Kayagaki N, Stowe IB, Lee BL, O’Rourke K, Anderson K, Warming S, et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature. 2015;526(7575):666–71.
  164. Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 2015;526(7575):660–5.
  165. Ding J, Wang K, Liu W, She Y, Sun Q, Shi J, et al. Pore-forming activity and structural autoinhibition of the gasdermin family. Nature. 2016;535(7610):111–6.
  166. Liu X, Zhang Z, Ruan J, Pan Y, Magupalli VG, Wu H, et al. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature. 2016;535(7610):153–8.
  167. Sborgi L, Rühl S, Mulvihill E, Pipercevic J, Heilig R, Stahlberg H, et al. GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death. EMBO J. 2016;35(16):1766–78.
  168. Aglietti RA, Estevez A, Gupta A, Ramirez MG, Liu PS, Kayagaki N, et al. GsdmD p30 elicited by caspase-11 during pyroptosis forms pores in membranes. Proc Natl Acad Sci USA. 2016;113(28):7858–63.
  169. Vance RE. The NAIP/NLRC4 inflammasomes. Curr Opin Immunol. 2015;32:84–9.
  170. Zhao Y, Shao F. The NAIP-NLRC4 inflammasome in innate immune detection of bacterial flagellin and type III secretion apparatus. Immunol Rev. 2015;265(1):85–102.
  171. Hu Z, Yan C, Liu P, Huang Z, Ma R, Zhang C, et al. Crystal structure of NLRC4 reveals its autoinhibition mechanism. Science. 2013;341(6142):172–5.
  172. Tenthorey JL, Kofoed EM, Daugherty MD, Malik HS, Vance RE. Molecular basis for specific recognition of bacterial ligands by NAIP/NLRC4 inflammasomes. Mol Cell. 2014;54(1):17–29.
  173. Lu A, Li Y, Schmidt FI, Yin Q, Chen S, Fu TM, et al. Molecular basis of caspase-1 polymerization and its inhibition by a new capping mechanism. Nat Struct Mol Biol. 2016;23(5):416–25.
  174. Schmidt FI, Lu A, Chen JW, Ruan J, Tang C, Wu H, et al. A single domain antibody fragment that recognizes the adaptor ASC defines the role of ASC domains in inflammasome assembly. J Exp Med. 2016;213(5):771–90.
  175. Canna SW, de Jesus AA, Gouni S, Brooks SR, Marrero B, Liu Y, et al. An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. Nat Genet. 2014;46(10):1140–6.
  176. Romberg N, Al Moussawi K, Nelson-Williams C, Stiegler AL, Loring E, Choi M, et al. Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflammation. Nat Genet. 2014;46(10):1135–9.
  177. Mariathasan S, Weiss DS, Newton K, McBride J, O’Rourke K, Roose-Girma M, et al. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature. 2006;440(7081):228–32.
  178. Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440(7081):237–41.
  179. Halle A, Hornung V, Petzold GC, Stewart CR, Monks BG, Reinheckel T, et al. The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat Immunol. 2008;9(8):857–65.
  180. Hafner-Bratkovič I, Benčina M, Fitzgerald KA, Golenbock D, Jerala R. NLRP3 inflammasome activation in macrophage cell lines by prion protein fibrils as the source of IL-1β and neuronal toxicity. Cell Mol Life Sci. 2012;69(24):4215–28.
  181. Hornung V, Ablasser A, Charrel-Dennis M, Bauernfeind F, Horvath G, Caffrey DR, et al. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature. 2009;458(7237):514–8.
  182. Fernandes-Alnemri T, Wu J, Yu JW, Datta P, Miller B, Jankowski W, et al. The pyroptosome: a supramolecular assembly of ASC dimers mediating inflammatory cell death via caspase-1 activation. Cell Death Differ. 2007;14(9):1590–604.
  183. Broz P, von Moltke J, Jones JW, Vance RE, Monack DM. Differential requirement for Caspase-1 autoproteolysis in pathogen-induced cell death and cytokine processing. Cell Host Microbe. 2010;8(6):471–83.
  184. Case CL, Shin S, Roy CR. Asc and Ipaf Inflammasomes direct distinct pathways for caspase-1 activation in response to Legionella pneumophila. Infect Immun. 2009;77(5):1981–91.
  185. Mariathasan S, Newton K, Monack DM, Vucic D, French DM, Lee WP, et al. Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature. 2004;430(6996):213–8.
  186. Hornung V, Bauernfeind F, Halle A, Samstad EO, Kono H, Rock KL, et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol. 2008;9(8):847–56.
  187. Adamczak S, Dale G, de Rivero Vaccari JP, Bullock MR, Dietrich WD, Keane RW. Inflammasome proteins in cerebrospinal fluid of brain-injured patients as biomarkers of functional outcome. J Neurosurg. 2012;117(6):1119–25.
  188. de Rivero Vaccari JP, Lotocki G, Alonso OF, Bramlett HM, Dietrich WD, Keane RW. Therapeutic neutralization of the NLRP1 inflammasome reduces the innate immune response and improves histopathology after traumatic brain injury. J Cereb Blood Flow Metab. 2009;29(7):1251–61.
  189. Kagan JC, Magupalli VG, Wu H. SMOCs: supramolecular organizing centres that control innate immunity. Nat Rev Immunol. 2014;14(12):821–6.
  190. Qiao Q, Yang C, Zheng C, Fontán L, David L, Yu X, et al. Structural architecture of the CARMA1/Bcl10/MALT1 signalosome: nucleation-induced filamentous assembly. Mol Cell. 2013;51(6):766–79.
  191. Yang J, Liu Z, Xiao TS. Post-translational regulation of inflammasomes. Cell Mol Immunol. 2017;14(1):65–79. [Epub ahead of print 2016 Jun 27]
  192. Agostini L, Martinon F, Burns K, McDermott MF, Hawkins PN, Tschopp J. NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity. 2004;20(3):319–25.