1932

Abstract

Peptides and proteins have been found to possess an inherent tendency to convert from their native functional states into intractable amyloid aggregates. This phenomenon is associated with a range of increasingly common human disorders, including Alzheimer and Parkinson diseases, type II diabetes, and a number of systemic amyloidoses. In this review, we describe this field of science with particular reference to the advances that have been made over the last decade in our understanding of its fundamental nature and consequences. We list the proteins that are known to be deposited as amyloid or other types of aggregates in human tissues and the disorders with which they are associated, as well as the proteins that exploit the amyloid motif to play specific functional roles in humans. In addition, we summarize the genetic factors that have provided insight into the mechanisms of disease onset. We describe recent advances in our knowledge of the structures of amyloid fibrils and their oligomeric precursors and of the mechanisms by which they are formed and proliferate to generate cellular dysfunction. We show evidence that a complex proteostasis network actively combats protein aggregation and that such an efficient system can fail in some circumstances and give rise to disease. Finally, we anticipate the development of novel therapeutic strategies with which to prevent or treat these highly debilitating and currently incurable conditions.

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2017-06-20
2024-04-24
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Literature Cited

  1. Chiti F, Dobson CM. 1.  2006. Protein misfolding, functional amyloid, and human disease. Annu. Rev. Biochem. 75:333–66 [Google Scholar]
  2. Guijarro JI, Sunde M, Jones JA, Campbell ID, Dobson CM. 2.  1998. Amyloid fibril formation by an SH3 domain. PNAS 95:4224–28 [Google Scholar]
  3. Chiti F, Webster P, Taddei N, Clark A, Stefani M. 3.  et al. 1999. Designing conditions for in vitro formation of amyloid protofilaments and fibrils. PNAS 96:3590–94 [Google Scholar]
  4. Fändrich M, Dobson CM. 4.  2002. The behaviour of polyamino acids reveals an inverse side chain effect in amyloid structure formation. EMBO J 21:5682–90 [Google Scholar]
  5. Adler-Abramovich L, Vaks L, Carny O, Trudler D, Magno A. 5.  et al. 2012. Phenylalanine assembly into toxic fibrils suggests amyloid etiology in phenylketonuria. Nat. Chem. Biol. 8:701–6 [Google Scholar]
  6. Knowles TP, Fitzpatrick AW, Meehan S, Mott HR, Vendruscolo M. 6.  et al. 2007. Role of intermolecular forces in defining material properties of protein nanofibrils. Science 318:1900–3 [Google Scholar]
  7. Cherny I, Gazit E. 7.  2008. Amyloids: not only pathological agents but also ordered nanomaterials. Angew. Chem. Int. Ed. Engl. 47:4062–69 [Google Scholar]
  8. Fowler DM, Koulov AV, Alory-Jost C, Marks MS, Balch WE, Kelly JW. 8.  2006. Functional amyloid formation within mammalian tissue. PLOS Biol 4:e6 [Google Scholar]
  9. Maji SK, Perrin MH, Sawaya MR, Jessberger S, Vadodaria K. 9.  et al. 2009. Functional amyloids as natural storage of peptide hormones in pituitary secretory granules. Science 325:328–32 [Google Scholar]
  10. Li J, McQuade T, Siemer AB, Napetschnig J, Moriwaki K. 10.  et al. 2012. The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis. Cell 150:339–50 [Google Scholar]
  11. Uversky VN. 11.  2013. Unusual biophysics of intrinsically disordered proteins. Biochim. Biophys. Acta 1834:932–51 [Google Scholar]
  12. Dobson CM. 12.  2003. Protein folding and misfolding. Nature 426:884–90 [Google Scholar]
  13. Lee J, Culyba EK, Powers ET, Kelly JW. 13.  2011. Amyloid-β forms fibrils by nucleated conformational conversion of oligomers. Nat. Chem. Biol. 7:602–9 [Google Scholar]
  14. Cremades N, Cohen SI, Deas E, Abramov AY, Chen AY. 14.  et al. 2012. Direct observation of the interconversion of normal and toxic forms of α-synuclein. Cell 149:1048–59 [Google Scholar]
  15. Eakin CM, Berman AJ, Miranker AD. 15.  2006. A native to amyloidogenic transition regulated by a backbone trigger. Nat. Struct. Mol. Biol. 13:202–8 [Google Scholar]
  16. Sekijima Y, Wiseman RL, Matteson J, Hammarström P, Miller SR. 16.  et al. 2005. The biological and chemical basis for tissue-selective amyloid disease. Cell 121:73–85 [Google Scholar]
  17. Bouchard M, Zurdo J, Nettleton EJ, Dobson CM, Robinson CV. 17.  2000. Formation of insulin amyloid fibrils followed by FTIR simultaneously with CD and electron microscopy. Protein Sci 9:1960–67 [Google Scholar]
  18. Serio TR, Cashikar AG, Kowal AS, Sawicki GJ, Moslehi JJ. 18.  et al. 2000. Nucleated conformational conversion and the replication of conformational information by a prion determinant. Science 289:1317–21 [Google Scholar]
  19. Bitan G, Kirkitadze MD, Lomakin A, Vollers SS, Benedek GB, Teplow DB. 19.  2003. Amyloid β-protein (Aβ) assembly: Aβ40 and Aβ42 oligomerize through distinct pathways. PNAS 100:330–35 [Google Scholar]
  20. Modler AJ, Gast K, Lutsch G, Damaschun G. 20.  2003. Assembly of amyloid protofibrils via critical oligomers—a novel pathway of amyloid formation. J. Mol. Biol. 325:135–48 [Google Scholar]
  21. Plakoutsi G, Bemporad F, Calamai M, Taddei N, Dobson CM, Chiti F. 21.  2005. Evidence for a mechanism of amyloid formation involving molecular reorganisation within native-like precursor aggregates. J. Mol. Biol. 351:910–22 [Google Scholar]
  22. Carulla N, Zhou M, Arimon M, Gairí M, Giralt E. 22.  et al. 2009. Experimental characterization of disordered and ordered aggregates populated during the process of amyloid fibril formation. PNAS 106:7828–33 [Google Scholar]
  23. Bleiholder C, Dupuis NF, Wyttenbach T, Bowers MT. 23.  2011. Ion mobility-mass spectrometry reveals a conformational conversion from random assembly to β-sheet in amyloid fibril formation. Nat Chem 3:172–77 [Google Scholar]
  24. Berger J, Hinglais N. 24.  1968. Intercapillary deposits of IgA-IgG. J. Urol. Nephrol. 74:694–95 [Google Scholar]
  25. Glenner GG, Terry W, Harada M, Isersky C, Page D. 25.  1971. Amyloid fibril proteins: proof of homology with immunoglobulin light chains by sequence analyses. Science 172:1150–51 [Google Scholar]
  26. Jimenez-Zepeda VH. 26.  2012. Light chain deposition disease: novel biological insights and treatment advances. Int. J. Lab. Hematol. 34:347–55 [Google Scholar]
  27. Usmani SM, Zirafi O, Müller JA, Sandi-Monroy NL, Yadav JK. 27.  et al. 2014. Direct visualization of HIV-enhancing endogenous amyloid fibrils in human semen. Nat. Commun. 5:3508 [Google Scholar]
  28. Monsellier E, Ramazzotti M, Taddei N, Chiti F. 28.  2008. Aggregation propensity of the human proteome. PLOS Comput. Biol. 4:e1000199 [Google Scholar]
  29. Ghiso JA, Holton J, Miravalle L, Calero M, Lashley T. 29.  et al. 2001. Systemic amyloid deposits in familial British dementia. J. Biol. Chem. 276:43909–14 [Google Scholar]
  30. Powers ET, Morimoto RI, Dillin A, Kelly JW, Balch WE. 30.  2009. Biological and chemical approaches to diseases of proteostasis deficiency. Annu. Rev. Biochem. 78:959–91 [Google Scholar]
  31. Koga H, Kaushik S, Cuervo AM. 31.  2011. Protein homeostasis and aging: the importance of exquisite quality control. Ageing Res. Rev. 10:205–15 [Google Scholar]
  32. Knowles TP, Vendruscolo M, Dobson CM. 32.  2014. The amyloid state and its association with protein misfolding diseases. Nat. Rev. Mol. Cell Biol. 15:384–96 [Google Scholar]
  33. Gajdusek DC, Gibbs CJ, Alpers M. 33.  1966. Experimental transmission of a Kuru-like syndrome to chimpanzees. Nature 209:794–96 [Google Scholar]
  34. Imran M, Mahmood S. 34.  2011. An overview of human prion diseases. Virol. J. 8:559 [Google Scholar]
  35. Will RG, Ironside JW, Zeidler M, Cousens SN, Estibeiro K. 35.  et al. 1996. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 347:921–25 [Google Scholar]
  36. Prusiner SB. 36.  2013. Biology and genetics of prions causing neurodegeneration. Annu. Rev. Genet. 47:601–23 [Google Scholar]
  37. Brettschneider J, Del Tredici K, Lee VM, Trojanowski JQ. 37.  2015. Spreading of pathology in neurodegenerative diseases: a focus on human studies. Nat. Rev. Neurosci. 16:109–20 [Google Scholar]
  38. Walker LC, Jucker M. 38.  2015. Neurodegenerative diseases: expanding the prion concept. Annu. Rev. Neurosci. 38:87–103 [Google Scholar]
  39. Aguzzi A, Lakkaraju AK. 39.  2016. Cell biology of prions and prionoids: a status report. Trends Cell Biol 26:40–51 [Google Scholar]
  40. Canet D, Last AM, Tito P, Sunde M, Spencer A. 40.  et al. 2002. Local cooperativity in the unfolding of an amyloidogenic variant of human lysozyme. Nat. Struct. Biol. 9:308–15 [Google Scholar]
  41. Dhulesia A, Cremades N, Kumita JR, Hsu ST, Mossuto MF. 41.  et al. 2010. Local cooperativity in an amyloidogenic state of human lysozyme observed at atomic resolution. J. Am. Chem. Soc. 132:15580–88 [Google Scholar]
  42. Ahn M, Hagan CL, Bernardo-Gancedo A, De Genst E, Newby FN. 42.  et al. 2016. The significance of the location of mutations for the native-state dynamics of human lysozyme. Biophys. J. 111:2358–67 [Google Scholar]
  43. Raimondi S, Guglielmi F, Giorgetti S, Di Gaetano S, Arciello A. 43.  et al. 2011. Effects of the known pathogenic mutations on the aggregation pathway of the amyloidogenic peptide of apolipoprotein A-I. J. Mol. Biol. 407:465–76 [Google Scholar]
  44. Gursky O, Mei X, Atkinson D. 44.  2012. The crystal structure of the C-terminal truncated apolipoprotein A-I sheds new light on amyloid formation by the N-terminal fragment. Biochemistry 51:10–18 [Google Scholar]
  45. Chen CD, Huff ME, Matteson J, Page L, Phillips R. 45.  et al. 2001. Furin initiates gelsolin familial amyloidosis in the Golgi through a defect in Ca2+ stabilization. EMBO J 20:6277–87 [Google Scholar]
  46. Page LJ, Suk JY, Huff ME, Lim HJ, Venable J. 46.  et al. 2005. Metalloendoprotease cleavage triggers gelsolin amyloidogenesis. EMBO J 24:4124–32 [Google Scholar]
  47. Solomon JP, Page LJ, Balch WE, Kelly JW. 47.  2012. Gelsolin amyloidosis: genetics, biochemistry, pathology and possible strategies for therapeutic intervention. Crit. Rev. Biochem. Mol. Biol. 47:282–96 [Google Scholar]
  48. Spillantini MG, Goedert M. 48.  2013. Tau pathology and neurodegeneration. Lancet Neurol 12:609–22 [Google Scholar]
  49. Niblock M, Gallo JM. 49.  2012. Tau alternative splicing in familial and sporadic tauopathies. Biochem. Soc. Trans. 40:677–80 [Google Scholar]
  50. Ancolio K, Dumanchin C, Barelli H, Warter JM, Brice A. 50.  et al. 1999. Unusual phenotypic alteration of β amyloid precursor protein (βAPP) maturation by a new Val-715 → Met βAPP-770 mutation responsible for probable early-onset Alzheimer's disease. PNAS 96:4119–24 [Google Scholar]
  51. De Jonghe C, Esselens C, Kumar-Singh S, Craessaerts K, Serneels S. 51.  et al. 2001. Pathogenic APP mutations near the γ-secretase cleavage site differentially affect Aβ secretion and APP C-terminal fragment stability. Hum. Mol. Genet. 10:1665–71 [Google Scholar]
  52. Farzan M, Schnitzler CE, Vasilieva N, Leung D, Choe H. 52.  2000. BACE2, a β-secretase homolog, cleaves at the β site and within the amyloid-β region of the amyloid-β precursor protein. PNAS 97:9712–17 [Google Scholar]
  53. Di Fede G, Catania M, Morbin M, Rossi G, Suardi S. 53.  et al. 2009. A recessive mutation in the APP gene with dominant-negative effect on amyloidogenesis. Science 323:1473–77 [Google Scholar]
  54. Nilsberth C, Westlind-Danielsson A, Eckman CB, Condron MM, Axelman K. 54.  et al. 2001. The ‘Arctic’ APP mutation (E693G) causes Alzheimer's disease by enhanced Aβ protofibril formation. Nat. Neurosci. 4:887–93 [Google Scholar]
  55. Tomiyama T, Nagata T, Shimada H, Teraoka R, Fukushima A. 55.  et al. 2008. A new amyloid β variant favoring oligomerization in Alzheimer's-type dementia. Ann. Neurol. 63:377–87 [Google Scholar]
  56. De Jonghe C, Zehr C, Yager D, Prada CM, Younkin S. 56.  et al. 1998. Flemish and Dutch mutations in amyloid β precursor protein have different effects on amyloid β secretion. Neurobiol. Dis. 5:281–86 [Google Scholar]
  57. Armstrong J, Boada M, Rey MJ, Vidal N, Ferrer I. 57.  2004. Familial Alzheimer disease associated with A713T mutation in APP. Neurosci. Lett. 370:241–43 [Google Scholar]
  58. Miravalle L, Tokuda T, Chiarle R, Giaccone G, Bugiani O. 58.  et al. 2000. Substitutions at codon 22 of Alzheimer's Aβ peptide induce diverse conformational changes and apoptotic effects in human cerebral endothelial cells. J. Biol. Chem. 275:27110–16 [Google Scholar]
  59. Zhou L, Brouwers N, Benilova I, Vandersteen A, Mercken M. 59.  et al. 2011. Amyloid precursor protein mutation E682K at the alternative β-secretase cleavage β′-site increases Aβ generation. EMBO Mol. Med. 3:291–302 [Google Scholar]
  60. Ghosh D, Sahay S, Ranjan P, Salot S, Mohite GM. 60.  et al. 2014. The newly discovered Parkinson's disease associated Finnish mutation (A53E) attenuates α-synuclein aggregation and membrane binding. Biochemistry 53:6419–21 [Google Scholar]
  61. Flagmeier P, Meisl G, Vendruscolo M, Knowles TP, Dobson CM. 61.  et al. 2016. Mutations associated with familial Parkinson's disease alter the initiation and amplification steps of α-synuclein aggregation. PNAS 113:10328–33 [Google Scholar]
  62. Caubet C, Bousset L, Clemmensen O, Sourigues Y, Bygum A. 62.  et al. 2010. A new amyloidosis caused by fibrillar aggregates of mutated corneodesmosin. FASEB J 24:3416–26 [Google Scholar]
  63. Vidal R, Frangione B, Rostagno A, Mead S, Révész T. 63.  et al. 1999. Systemic amyloid deposits in familial British dementia. Nature 399:776–81 [Google Scholar]
  64. Vidal R, Révész T, Rostagno A, Kim E, Holton JL. 64.  et al. 2000. A decamer duplication in the 3′ region of the BRI gene originates an amyloid peptide that is associated with dementia in a Danish kindred. PNAS 97:4920–25 [Google Scholar]
  65. Benson MD, Liepnieks JJ, Yazaki M, Yamashita T, Hamidi Asl K. 65.  et al. 2001. A new human hereditary amyloidosis: the result of a stop-codon mutation in the apolipoprotein AII gene. Genomics 72:272–77 [Google Scholar]
  66. De Gracia R, Fernández EJ, Riñón C, Selgas R, Garcia-Bustos J. 66.  2006. Hereditary renal amyloidosis associated with a novel mutation in the apolipoprotein AII gene. QJM 99:274 [Google Scholar]
  67. Srinivasan R, Jones EM, Liu K, Ghiso J, Marchant RE, Zagorski MG. 67.  2003. pH-dependent amyloid and protofibril formation by the ABri peptide of familial British dementia. J. Mol. Biol. 333:1003–23 [Google Scholar]
  68. von Mikecz A. 68.  2014. Pathology and function of nuclear amyloid. Protein homeostasis matters. Nucleus 5:311–17 [Google Scholar]
  69. Rovelet-Lecrux A, Hannequin D, Raux G, Le Meur N, Laquerrière A. 69.  et al. 2006. APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy. Nat. Genet. 38:24–26 [Google Scholar]
  70. Singleton AB, Farrer M, Johnson J, Singleton A, Hague S. 70.  et al. 2003. α-Synuclein locus triplication causes Parkinson's disease. Science 302:841 [Google Scholar]
  71. Chartier-Harlin MC, Kachergus J, Roumier C, Mouroux V, Douay X. 71.  et al. 2004. α-Synuclein locus duplication as a cause of familial Parkinson's disease. Lancet 364:1167–69 [Google Scholar]
  72. Paravastu AK, Leapman RD, Yau WM, Tycko R. 72.  2008. Molecular structural basis for polymorphism in Alzheimer's β-amyloid fibrils. PNAS 105:18349–54 [Google Scholar]
  73. Wasmer C, Lange A, Van Melckebeke H, Siemer AB, Riek R, Meier BH. 73.  2008. Amyloid fibrils of the HET-s(218–289) prion form a β solenoid with a triangular hydrophobic core. Science 319:1523–26 [Google Scholar]
  74. Sunde M, Blake C. 74.  1997. The structure of amyloid fibrils by electron microscopy and X-ray diffraction. Adv. Protein Chem. 50:123–59 [Google Scholar]
  75. Zandomeneghi G, Krebs MR, McCammon MG, Fändrich M. 75.  2004. FTIR reveals structural differences between native β-sheet proteins and amyloid fibrils. Protein Sci 13:3314–21 [Google Scholar]
  76. Eisenberg D, Jucker M. 76.  2012. The amyloid state of proteins in human diseases. Cell 148:1188–203 [Google Scholar]
  77. Nilsson MR. 77.  2004. Techniques to study amyloid fibril formation in vitro. Methods 34:151–60 [Google Scholar]
  78. Mathis CA, Mason NS, Lopresti BJ, Klunk WE. 78.  2012. Development of positron emission tomography β-amyloid plaque imaging agents. Semin. Nucl. Med. 42:423–32 [Google Scholar]
  79. Gazit E. 79.  2002. The “correctly” folded state of proteins: Is it a metastable state?. Angew. Chem. Int. Ed. Engl. 41:257–69 [Google Scholar]
  80. Baldwin AJ, Knowles TP, Tartaglia GG, Fitzpatrick AW, Devlin GL. 80.  et al. 2011. Metastability of native proteins and the phenomenon of amyloid formation. J. Am. Chem. Soc. 133:14160–63 [Google Scholar]
  81. Balchin D, Hayer-Hartl M, Hartl FU. 81.  2016. In vivo aspects of protein folding and quality control. Science 353:aac4354 [Google Scholar]
  82. Petkova AT, Yau WM, Tycko R. 82.  2006. Experimental constraints on quaternary structure in Alzheimer's β-amyloid fibrils. Biochemistry 45:498–512 [Google Scholar]
  83. Bertini I, Gonnelli L, Luchinat C, Mao J, Nesi A. 83.  2011. A new structural model of Aβ40 fibrils. J. Am. Chem. Soc. 133:16013–22 [Google Scholar]
  84. Lu JX, Qiang W, Yau WM, Schwieters CD, Meredith SC, Tycko R. 84.  2013. Molecular structure of β-amyloid fibrils in Alzheimer's disease brain tissue. Cell 154:1257–68 [Google Scholar]
  85. Colvin MT, Silvers R, Ni QZ, Can TV, Sergeyev I. 85.  et al. 2016. Atomic resolution structure of monomorphic Aβ42 amyloid fibrils. J. Am. Chem. Soc. 138:9663–74 [Google Scholar]
  86. Luca S, Yau WM, Leapman R, Tycko R. 86.  2007. Peptide conformation and supramolecular organization in amylin fibrils: constraints from solid-state NMR. Biochemistry 46:13505–22 [Google Scholar]
  87. Weirich F, Gremer L, Mirecka EA, Schiefer S, Hoyer W, Heise H. 87.  2016. Structural characterization of fibrils from recombinant human islet amyloid polypeptide by solid-state NMR: The central FGAILS segment is part of the β-sheet core. PLOS ONE 11:e0161243 [Google Scholar]
  88. Davies HA, Madine J, Middleton DA. 88.  2015. Comparisons with amyloid-β reveal an aspartate residue that stabilizes fibrils of the aortic amyloid peptide medin. J. Biol. Chem. 290:7791–803 [Google Scholar]
  89. Hoop CL, Lin HK, Kar K, Magyarfalvi G, Lamley JM. 89.  et al. 2016. Huntingtin exon 1 fibrils feature an interdigitated β-hairpin-based polyglutamine core. PNAS 113:1546–51 [Google Scholar]
  90. Helmus JJ, Surewicz K, Apostol MI, Surewicz WK, Jaroniec CP. 90.  2011. Intermolecular alignment in Y145Stop human prion protein amyloid fibrils probed by solid-state NMR spectroscopy. J. Am. Chem. Soc. 133:13934–37 [Google Scholar]
  91. Müller H, Brener O, Andreoletti O, Piechatzek T, Willbold D. 91.  et al. 2014. Progress towards structural understanding of infectious sheep PrP-amyloid. Prion 8:344–58 [Google Scholar]
  92. Yang Y, Petkova A, Huang K, Xu B, Hua QX. 92.  et al. 2010. An Achilles’ heel in an amyloidogenic protein and its repair: insulin fibrillation and therapeutic design. J. Biol. Chem. 285:10806–21 [Google Scholar]
  93. Bateman DA, Tycko R, Wickner RB. 93.  2011. Experimentally derived structural constraints for amyloid fibrils of wild-type transthyretin. Biophys. J. 101:2485–92 [Google Scholar]
  94. Daebel V, Chinnathambi S, Biernat J, Schwalbe M, Habenstein B. 94.  et al. 2012. β-Sheet core of tau paired helical filaments revealed by solid-state NMR. J. Am. Chem. Soc. 134:13982–89 [Google Scholar]
  95. Itoh-Watanabe H, Kamihira-Ishijima M, Javkhlantugs N, Inoue R, Itoh Y. 95.  et al. 2013. Role of aromatic residues in amyloid fibril formation of human calcitonin by solid-state 13C NMR and molecular dynamics simulation. Phys. Chem. Chem. Phys. 15:8890–901 [Google Scholar]
  96. Su Y, Sarell CJ, Eddy MT, Debelouchina GT, Andreas LB. 96.  et al. 2014. Secondary structure in the core of amyloid fibrils formed from human β2m and its truncated variant ΔN6. J. Am. Chem. Soc. 136:6313–25 [Google Scholar]
  97. Heise H, Hoyer W, Becker S, Andronesi OC, Riedel D, Baldus M. 97.  2005. Molecular-level secondary structure, polymorphism, and dynamics of full-length α-synuclein fibrils studied by solid-state NMR. PNAS 102:15871–76 [Google Scholar]
  98. Vilar M, Chou HT, Lührs T, Maji SK, Riek-Loher D. 98.  et al. 2008. The fold of α-synuclein fibrils. PNAS 105:8637–42 [Google Scholar]
  99. Comellas G, Lemkau LR, Nieuwkoop AJ, Kloepper KD, Ladror DT. 99.  et al. 2011. Structured regions of α-synuclein fibrils include the early-onset Parkinson's disease mutation sites. J. Mol. Biol. 411:881–95 [Google Scholar]
  100. Gath J, Bousset L, Habenstein B, Melki R, Böckmann A, Meier BH. 100.  2014. Unlike twins: an NMR comparison of two α-synuclein polymorphs featuring different toxicity. PLOS ONE 9:e90659 [Google Scholar]
  101. Gath J, Bousset L, Habenstein B, Melki R, Meier BH, Böckmann A. 101.  2014. Yet another polymorph of α-synuclein: solid-state sequential assignments. Biomol. NMR Assign. 8:395–404 [Google Scholar]
  102. Tuttle MD, Comellas G, Nieuwkoop AJ, Covell DJ, Berthold DA. 102.  et al. 2016. Solid-state NMR structure of a pathogenic fibril of full-length human α-synuclein. Nat. Struct. Mol. Biol. 23:409–15 [Google Scholar]
  103. Van Melckebeke H, Wasmer C, Lange A, Ab E, Loquet A. 103.  et al. 2010. Atomic-resolution three-dimensional structure of HET-s(218–289) amyloid fibrils by solid-state NMR spectroscopy. J. Am. Chem. Soc. 132:13765–75 [Google Scholar]
  104. Vázquez-Fernández E, Vos MR, Afanasyev P, Cebey L, Sevillano AM. 104.  et al. 2016. The structural architecture of an infectious mammalian prion using electron cryomicroscopy. PLOS Pathog 12:e1005835 [Google Scholar]
  105. Fitzpatrick AW, Debelouchina GT, Bayro MJ, Clare DK, Caporini MA. 105.  et al. 2013. Atomic structure and hierarchical assembly of a cross-β amyloid fibril. PNAS 110:5468–73 [Google Scholar]
  106. Makin OS, Atkins E, Sikorski P, Johansson J, Serpell LC. 106.  2005. Molecular basis for amyloid fibril formation and stability. PNAS 102:315–20 [Google Scholar]
  107. Sikorski P, Atkins E. 107.  2005. New model for crystalline polyglutamine assemblies and their connection with amyloid fibrils. Biomacromolecules 6:425–32 [Google Scholar]
  108. Morris KL, Serpell LC. 108.  2012. X-ray fibre diffraction studies of amyloid fibrils. Methods Mol. Biol. 849:121–35 [Google Scholar]
  109. Rodriguez JA, Ivanova MI, Sawaya MR, Cascio D, Reyes FE. 109.  et al. 2015. Structure of the toxic core of α-synuclein from invisible crystals. Nature 525:486–90 [Google Scholar]
  110. Serag AA, Altenbach C, Gingery M, Hubbell WL, Yeates TO. 110.  2002. Arrangement of subunits and ordering of β-strands in an amyloid sheet. Nat. Struct. Biol. 9:734–39 [Google Scholar]
  111. Olofsson A, Ippel JH, Wijmenga SS, Lundgren E, Ohman A. 111.  2004. Probing solvent accessibility of transthyretin amyloid by solution NMR spectroscopy. J. Biol. Chem. 279:5699–707 [Google Scholar]
  112. Lim KH, Dasari AK, Hung I, Gan Z, Kelly JW. 112.  et al. 2016. Solid-state NMR studies reveal native-like β-sheet structures in transthyretin amyloid. Biochemistry 55:5272–78 [Google Scholar]
  113. Elam JS, Taylor AB, Strange R, Antonyuk S, Doucette PA. 113.  et al. 2003. Amyloid-like filaments and water-filled nanotubes formed by SOD1 mutant proteins linked to familial ALS. Nat. Struct. Biol. 10:461–67 [Google Scholar]
  114. Janowski R, Kozak M, Abrahamson M, Grubb A, Jaskolski M. 114.  2005. 3D domain-swapped human cystatin C with amyloidlike intermolecular β-sheets. Proteins 61:570–78 [Google Scholar]
  115. Sambashivan S, Liu Y, Sawaya MR, Gingery M, Eisenberg D. 115.  2005. Amyloid-like fibrils of ribonuclease A with three-dimensional domain-swapped and native-like structure. Nature 437:266–69 [Google Scholar]
  116. Guo Z, Eisenberg D. 116.  2006. Runaway domain swapping in amyloid-like fibrils of T7 endonuclease I. PNAS 103:8042–47 [Google Scholar]
  117. Petkova AT, Leapman RD, Guo Z, Yau WM, Mattson MP, Tycko R. 117.  2005. Self-propagating, molecular-level polymorphism in Alzheimer's β-amyloid fibrils. Science 307:262–65 [Google Scholar]
  118. Surmacz-Chwedoruk W, Nieznańska H, Wójcik S, Dzwolak W. 118.  2012. Cross-seeding of fibrils from two types of insulin induces new amyloid strains. Biochemistry 51:9460–69 [Google Scholar]
  119. Peelaerts W, Bousset L, Van der Perren A, Moskalyuk A, Pulizzi R. 119.  et al. 2015. α-Synuclein strains cause distinct synucleinopathies after local and systemic administration. Nature 522:340–44 [Google Scholar]
  120. Collinge J, Clarke AR. 120.  2007. A general model of prion strains and their pathogenicity. Science 318:930–36 [Google Scholar]
  121. Török M, Milton S, Kayed R, Wu P, McIntire T. 121.  et al. 2002. Structural and dynamic features of Alzheimer's Aβ peptide in amyloid fibrils studied by site-directed spin labeling. J. Biol. Chem. 277:40810–15 [Google Scholar]
  122. Lührs T, Ritter C, Adrian M, Riek-Loher D, Bohrmann B. 122.  et al. 2005. 3D structure of Alzheimer's amyloid-β(1–42) fibrils. PNAS 102:17342–47 [Google Scholar]
  123. Der-Sarkissian A, Jao CC, Chen J, Langen R. 123.  2003. Structural organization of α-synuclein fibrils studied by site-directed spin labeling. J. Biol. Chem. 278:37530–35 [Google Scholar]
  124. Chen M, Margittai M, Chen J, Langen R. 124.  2007. Investigation of α-synuclein fibril structure by site-directed spin labeling. J. Biol. Chem. 282:24970–79 [Google Scholar]
  125. Margittai M, Langen R. 125.  2004. Template-assisted filament growth by parallel stacking of tau. PNAS 101:10278–83 [Google Scholar]
  126. Bedrood S, Li Y, Isas JM, Hegde BG, Baxa U. 126.  et al. 2012. Fibril structure of human islet amyloid polypeptide. J. Biol. Chem. 287:5235–41 [Google Scholar]
  127. Ladner CL, Chen M, Smith DP, Platt GW, Radford SE, Langen R. 127.  2010. Stacked sets of parallel, in-register β-strands of β2-microglobulin in amyloid fibrils revealed by site-directed spin labeling and chemical labeling. J. Biol. Chem. 285:17137–47 [Google Scholar]
  128. Tycko R, Savtchenko R, Ostapchenko V, Makarava N, Baskakov I. 128.  2010. The α-helical C-terminal domain of full-length recombinant PrP converts to an in-register parallel β-sheet structure in PrP fibrils: evidence from solid state nuclear magnetic resonance. Biochemistry 49:9488–97 [Google Scholar]
  129. Qiang W, Yau WM, Tycko R. 129.  2011. Structural evolution of Iowa mutant β-amyloid fibrils from polymorphic to homogeneous states under repeated seeded growth. J. Am. Chem. Soc. 133:4018–29 [Google Scholar]
  130. Belli M, Ramazzotti M, Chiti F. 130.  2011. Prediction of amyloid aggregation in vivo. EMBO Rep 12:657–63 [Google Scholar]
  131. Pawar AP, Dubay KF, Zurdo J, Chiti F, Vendruscolo M, Dobson CM. 131.  2005. Prediction of “aggregation-prone” and “aggregation-susceptible” regions in proteins associated with neurodegenerative diseases. J. Mol. Biol. 350:379–92 [Google Scholar]
  132. Tartaglia GG, Pawar AP, Campioni S, Dobson CM, Chiti F, Vendruscolo M. 132.  2008. Prediction of aggregation-prone regions in structured proteins. J. Mol. Biol. 380:425–36 [Google Scholar]
  133. Zambrano R, Jamroz M, Szczasiuk A, Pujols J, Kmiecik S, Ventura S. 133.  2015. AGGRESCAN3D (A3D): server for prediction of aggregation properties of protein structures. Nucleic Acids Res 43:W306–13 [Google Scholar]
  134. Morozova OA, March ZM, Robinson AS, Colby DW. 134.  2013. Conformational features of tau fibrils from Alzheimer's disease brain are faithfully propagated by unmodified recombinant protein. Biochemistry 52:6960–67 [Google Scholar]
  135. Knowles TP, Waudby CA, Devlin GL, Cohen SI, Aguzzi A. 135.  et al. 2009. An analytical solution to the kinetics of breakable filament assembly. Science 326:1533–37 [Google Scholar]
  136. Jarrett JT, Berger EP, Lansbury PT Jr. 136.  1993. The carboxy terminus of the β amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer's disease. Biochemistry 32:4693–97 [Google Scholar]
  137. Ferrone F. 137.  1999. Analysis of protein aggregation kinetics. Methods Enzymol 309:256–74 [Google Scholar]
  138. Morris AM, Watzky MA, Finke RG. 138.  2009. Protein aggregation kinetics, mechanism, and curve-fitting: a review of the literature. Biochim. Biophys. Acta 1794:375–97 [Google Scholar]
  139. Arosio P, Knowles TP, Linse S. 139.  2015. On the lag phase in amyloid fibril formation. Phys. Chem. Chem. Phys. 17:7606–18 [Google Scholar]
  140. Chen S, Ferrone FA, Wetzel R. 140.  2002. Huntington's disease age-of-onset linked to polyglutamine aggregation nucleation. PNAS 99:11884–89 [Google Scholar]
  141. Ferrone FA. 141.  2015. Assembly of Aβ proceeds via monomeric nuclei. J. Mol. Biol. 427:287–90 [Google Scholar]
  142. Masel J, Jansen VAA, Nowak MA. 142.  1999. Quantifying the kinetic parameters of prion replication. Biophys. Chem. 77:139–52 [Google Scholar]
  143. Uversky VN, Li J, Fink AL. 143.  2001. Evidence for a partially folded intermediate in α-synuclein fibril formation. J. Biol. Chem. 276:10737–44 [Google Scholar]
  144. Bhattacharyya AM, Thakur AK, Wetzel R. 144.  2005. Polyglutamine aggregation nucleation: thermodynamics of a highly unfavorable protein folding reaction. PNAS 102:15400–5 [Google Scholar]
  145. Pease LF 3rd, Sorci M, Guha S, Tsai DH, Zachariah MR. 145.  et al. 2010. Probing the nucleus model for oligomer formation during insulin amyloid fibrillogenesis. Biophys. J. 99:3979–85 [Google Scholar]
  146. Cerdà-Costa N, De la Arada I, Avilés FX, Arrondo JL, Villegas S. 146.  2009. Influence of aggregation propensity and stability on amyloid fibril formation as studied by Fourier transform infrared spectroscopy and two-dimensional COS analysis. Biochemistry 48:10582–90 [Google Scholar]
  147. Almstedt K, Nyström S, Nilsson KP, Hammarström P. 147.  2009. Amyloid fibrils of human prion protein are spun and woven from morphologically disordered aggregates. Prion 3:224–35 [Google Scholar]
  148. Thakur AK, Jayaraman M, Mishra R, Thakur M, Chellgren VM. 148.  et al. 2009. Polyglutamine disruption of the huntingtin exon 1 N terminus triggers a complex aggregation mechanism. Nat. Struct. Mol. Biol. 16:380–89 [Google Scholar]
  149. Wei L, Jiang P, Xu W, Li H, Zhang H. 149.  et al. 2011. The molecular basis of distinct aggregation pathways of islet amyloid polypeptide. J. Biol. Chem. 286:6291–300 [Google Scholar]
  150. Zou Y, Hao W, Li H, Gao Y, Sun Y, Ma G. 150.  2014. New insight into amyloid fibril formation of hen egg white lysozyme using a two-step temperature-dependent FTIR approach. J. Phys. Chem. B 118:9834–43 [Google Scholar]
  151. Chiti F, Dobson CM. 151.  2009. Amyloid formation by globular proteins under native conditions. Nat. Chem. Biol. 5:15–22 [Google Scholar]
  152. Banci L, Bertini I, D'Amelio N, Gaggelli E, Libralesso E. 152.  et al. 2005. Fully metallated S134N Cu,Zn-superoxide dismutase displays abnormal mobility and intermolecular contacts in solution. J. Biol. Chem. 280:35815–21 [Google Scholar]
  153. Bemporad F, Chiti F. 153.  2009. “Native-like aggregation” of the acylphosphatase from Sulfolobus solfataricus and its biological implications. FEBS Lett 583:2630–38 [Google Scholar]
  154. Soldi G, Bemporad F, Torrassa S, Relini A, Ramazzotti M. 154.  et al. 2005. Amyloid formation of a protein in the absence of initial unfolding and destabilization of the native state. Biophys. J. 89:4234–44 [Google Scholar]
  155. Neudecker P, Robustelli P, Cavalli A, Walsh P, Lundström P. 155.  et al. 2012. Structure of an intermediate state in protein folding and aggregation. Science 336:362–66 [Google Scholar]
  156. Garcia-Pardo J, Graña-Montes R, Fernandez-Mendez M, Ruyra A, Roher N. 156.  et al. 2014. Amyloid formation by human carboxypeptidase D transthyretin-like domain under physiological conditions. J. Biol. Chem. 289:33783–96 [Google Scholar]
  157. Masino L, Nicastro G, Calder L, Vendruscolo M, Pastore A. 157.  2011. Functional interactions as a survival strategy against abnormal aggregation. FASEB J 25:45–54 [Google Scholar]
  158. Ferrolino MC, Zhuravleva A, Budyak IL, Krishnan B, Gierasch LM. 158.  2013. Delicate balance between functionally required flexibility and aggregation risk in a β-rich protein. Biochemistry 52:8843–54 [Google Scholar]
  159. Kumar S, Udgaonkar JB. 159.  2009. Structurally distinct amyloid protofibrils form on separate pathways of aggregation of a small protein. Biochemistry 48:6441–49 [Google Scholar]
  160. Dinner AR, Šali A, Smith LJ, Dobson CM, Karplus M. 160.  2000. Understanding protein folding via the free-energy surfaces from theory and experiment. Trends Biochem. Sci. 7:331–39 [Google Scholar]
  161. Padrick SB, Miranker AD. 161.  2002. Islet amyloid: Phase partitioning and secondary nucleation are central to the mechanism of fibrillogenesis. Biochemistry 41:4694–703 [Google Scholar]
  162. Ramachandran G, Udgaonkar JB. 162.  2012. Evidence for the existence of a secondary pathway for fibril growth during the aggregation of tau. J. Mol. Biol. 421:296–314 [Google Scholar]
  163. Cohen SI, Linse S, Luheshi LM, Hellstrand E, White DA. 163.  et al. 2013. Proliferation of amyloid-β42 aggregates occurs through a secondary nucleation mechanism. PNAS 110:9758–63 [Google Scholar]
  164. Meisl G, Yang X, Hellstrand E, Frohm B, Kirkegaard JB. 164.  et al. 2014. Differences in nucleation behavior underlie the contrasting aggregation kinetics of the Aβ40 and Aβ42 peptides. PNAS 111:9384–89 [Google Scholar]
  165. Buell AK, Galvagnion C, Gaspar R, Sparr E, Vendruscolo M. 165.  et al. 2014. Solution conditions determine the relative importance of nucleation and growth processes in α-synuclein aggregation. PNAS 111:7671–76 [Google Scholar]
  166. Kakkar V, Månsson C, de Mattos EP, Bergink S, van der Zwaag M. 166.  et al. 2016. The S/T-rich motif in the DNAJB6 chaperone delays polyglutamine aggregation and the onset of disease in a mouse model. Mol. Cell 62:272–83 [Google Scholar]
  167. Xu LQ, Wu S, Buell AK, Cohen SI, Chen LJ. 167.  et al. 2013. Influence of specific HSP70 domains on fibril formation of the yeast prion protein Ure2. Philos. Trans. R. Soc. B. 368:20110410 [Google Scholar]
  168. Galvagnion C, Buell AK, Meisl G, Michaels TC, Vendruscolo M. 168.  et al. 2015. Lipid vesicles trigger α-synuclein aggregation by stimulating primary nucleation. Nat. Chem. Biol. 11:229–34 [Google Scholar]
  169. Arosio P, Michaels TC, Linse S, Månsson C, Emanuelsson C. 169.  et al. 2016. Kinetic analysis reveals the diversity of microscopic mechanisms through which molecular chaperones suppress amyloid formation. Nat. Commun. 7:10948 [Google Scholar]
  170. Kayed R, Head E, Thompson JL, McIntire TM, Milton SC. 170.  et al. 2003. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 300:486–89 [Google Scholar]
  171. Lesné S, Koh MT, Kotilinek L, Kayed R, Glabe CG. 171.  et al. 2006. A specific amyloid-β protein assembly in the brain impairs memory. Nature 440:352–57 [Google Scholar]
  172. Lambert MP, Barlow AK, Chromy BA, Edwards C, Freed R. 172.  et al. 1998. Diffusible, nonfibrillar ligands derived from Aβ1–42 are potent central nervous system neurotoxins. PNAS 95:6448–53 [Google Scholar]
  173. Kayed R, Head E, Sarsoza F, Saing T, Cotman CW. 173.  et al. 2007. Fibril specific, conformation dependent antibodies recognize a generic epitope common to amyloid fibrils and fibrillar oligomers that is absent in prefibrillar oligomers. Mol. Neurodegener. 2:18 [Google Scholar]
  174. Kayed R, Pensalfini A, Margol L, Sokolov Y, Sarsoza F. 174.  et al. 2009. Annular protofibrils are a structurally and functionally distinct type of amyloid oligomer. J. Biol. Chem. 284:4230–37 [Google Scholar]
  175. Barghorn S, Nimmrich V, Striebinger A, Krantz C, Keller P. 175.  et al. 2005. Globular amyloid β-peptide1–42 oligomer—a homogenous and stable neuropathological protein in Alzheimer's disease. J. Neurochem. 95:834–47 [Google Scholar]
  176. Hoshi M, Sato M, Matsumoto S, Noguchi A, Yasutake K. 176.  et al. 2003. Spherical aggregates of β-amyloid (amylospheroid) show high neurotoxicity and activate tau protein kinase I/glycogen synthase kinase-3β. PNAS 100:6370–75 [Google Scholar]
  177. Chimon S, Shaibat MA, Jones CR, Calero DC, Aizezi B, Ishii Y. 177.  2007. Evidence of fibril-like β-sheet structures in a neurotoxic amyloid intermediate of Alzheimer's β-amyloid. Nat. Struct. Mol. Biol. 14:1157–64 [Google Scholar]
  178. Ahmed M, Davis J, Aucoin D, Sato T, Ahuja S. 178.  et al. 2010. Structural conversion of neurotoxic amyloid-beta1–42 oligomers to fibrils. Nat. Struct. Mol. Biol. 17:561–67 [Google Scholar]
  179. Podlisny MB, Ostaszewski BL, Squazzo SL, Koo EH, Rydell RE. 179.  et al. 1995. Aggregation of secreted amyloid β-protein into sodium dodecyl sulfate-stable oligomers in cell culture. J. Biol. Chem. 270:9564–70 [Google Scholar]
  180. Harper JD, Wong SS, Lieber CM, Lansbury PT. 180.  1997. Observation of metastable Aβ amyloid protofibrils by atomic force microscopy. Chem. Biol. 4:119–25 [Google Scholar]
  181. Stroud JC, Liu C, Teng PK, Eisenberg D. 181.  2012. Toxic fibrillar oligomers of amyloid-β have cross-β structure. PNAS 109:7717–22 [Google Scholar]
  182. Parthasarathy S, Inoue M, Xiao Y, Matsumura Y, Nabeshima Y. 182.  et al. 2015. Structural insight into an Alzheimer's brain-derived spherical assembly of amyloid β by solid-state NMR. J. Am. Chem. Soc. 137:6480–83 [Google Scholar]
  183. O'Nuallain B, Freir DB, Nicoll AJ, Risse E, Ferguson N. 183.  et al. 2010. Amyloid β-protein dimers rapidly form stable synaptotoxic protofibrils. J. Neurosci. 30:14411–19 [Google Scholar]
  184. Matsumura S, Shinoda K, Yamada M, Yokojima S, Inoue M. 184.  et al. 2011. Two distinct amyloid β-protein (Aβ) assembly pathways leading to oligomers and fibrils identified by combined fluorescence correlation spectroscopy, morphology, and toxicity analyses. J. Biol. Chem. 286:11555–62 [Google Scholar]
  185. Fu Z, Aucoin D, Davis J, Van Nostrand WE, Smith SO. 185.  2015. Mechanism of nucleated conformational conversion of Aβ42. Biochemistry 54:4197–207 [Google Scholar]
  186. Lasagna-Reeves CA, Glabe CG, Kayed R. 186.  2011. Amyloid-β annular protofibrils evade fibrillar fate in Alzheimer disease brain. J. Biol. Chem. 286:22122–30 [Google Scholar]
  187. Chen SW, Drakulic S, Deas E, Ouberai M, Aprile FA. 187.  et al. 2015. Structural characterization of toxic oligomers that are kinetically trapped during α-synuclein fibril formation. PNAS 112:E1994–2003 [Google Scholar]
  188. Gallea JI, Celej MS. 188.  2014. Structural insights into amyloid oligomers of the Parkinson disease-related protein α-synuclein. J. Biol. Chem. 289:26733–42 [Google Scholar]
  189. Lorenzen N, Nielsen SB, Buell AK, Kaspersen JD, Arosio P. 189.  et al. 2014. The role of stable α-synuclein oligomers in the molecular events underlying amyloid formation. J. Am. Chem. Soc. 136:3859–68 [Google Scholar]
  190. Zraika S, Hull RL, Verchere CB, Clark A, Potter KJ. 190.  et al. 2010. Toxic oligomers and islet beta cell death: guilty by association or convicted by circumstantial evidence?. Diabetologia 53:1046–56 [Google Scholar]
  191. Almeida MR, Saraiva MJ. 191.  2012. Clearance of extracellular misfolded proteins in systemic amyloidosis: experience with transthyretin. FEBS Lett 586:2891–96 [Google Scholar]
  192. Kastritis E, Dimopoulos MA. 192.  2016. Recent advances in the management of AL amyloidosis. Br. J. Haematol. 172:170–86 [Google Scholar]
  193. Roberts HL, Brown DR. 193.  2015. Seeking a mechanism for the toxicity of oligomeric α-synuclein. Biomolecules 5:282–305 [Google Scholar]
  194. Benilova I, Karran E, De Strooper B. 194.  2012. The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes. Nat. Neurosci. 15:349–57 [Google Scholar]
  195. Guerrero-Muñoz MJ, Gerson J, Castillo-Carranza DL. 195.  2015. Tau oligomers: the toxic player at synapses in Alzheimer's disease. Front. Cell. Neurosci. 9:464 [Google Scholar]
  196. Labbadia J, Morimoto RI. 196.  2015. The biology of proteostasis in aging and disease. Annu. Rev. Biochem. 84:435–64 [Google Scholar]
  197. Martins IC, Kuperstein I, Wilkinson H, Maes E, Vanbrabant M. 197.  et al. 2008. Lipids revert inert Aβ amyloid fibrils to neurotoxic protofibrils that affect learning in mice. EMBO J 27:224–33 [Google Scholar]
  198. Koffie RM, Meyer-Luehmann M, Hashimoto T, Adams KW, Mielke ML. 198.  et al. 2009. Oligomeric amyloid β associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques. PNAS 106:4012–17 [Google Scholar]
  199. Campioni S, Mannini B, Zampagni M, Pensalfini A, Parrini C. 199.  et al. 2010. A causative link between the structure of aberrant protein oligomers and their toxicity. Nat. Chem. Biol. 6:140–47 [Google Scholar]
  200. Ladiwala AR, Litt J, Kane RS, Aucoin DS, Smith SO. 200.  et al. 2012. Conformational differences between two amyloid β oligomers of similar size and dissimilar toxicity. J. Biol. Chem. 287:24765–73 [Google Scholar]
  201. Krishnan R, Goodman JL, Mukhopadhyay S, Pacheco CD, Lemke EA. 201.  et al. 2012. Conserved features of intermediates in amyloid assembly determine their benign or toxic states. PNAS 109:11172–77 [Google Scholar]
  202. Bolognesi B, Kumita JR, Barros TP, Esbjorner EK, Luheshi LM. 202.  et al. 2010. ANS binding reveals common features of cytotoxic amyloid species. ACS Chem. Biol. 5:735–40 [Google Scholar]
  203. Olzscha H, Schermann SM, Woerner AC, Pinkert S, Hecht MH. 203.  et al. 2011. Amyloid-like aggregates sequester numerous metastable proteins with essential cellular functions. Cell 144:67–78 [Google Scholar]
  204. Lambert MP, Viola KL, Chromy BA, Chang L, Morgan TE. 204.  et al. 2001. Vaccination with soluble Aβ oligomers generates toxicity-neutralizing antibodies. J. Neurochem. 79:595–605 [Google Scholar]
  205. Gong Y, Chang L, Viola KL, Lacor PN, Lambert MP. 205.  et al. 2003. Alzheimer's disease-affected brain: Presence of oligomeric Aβ ligands (ADDLs) suggests a molecular basis for reversible memory loss. PNAS 100:10417–22 [Google Scholar]
  206. Ojha J, Masilamoni G, Dunlap D, Udoff RA, Cashikar AG. 206.  2011. Sequestration of toxic oligomers by HspB1 as a cytoprotective mechanism. Mol. Cell. Biol. 31:3146–57 [Google Scholar]
  207. Mannini B, Cascella R, Zampagni M, van Waarde-Verhagen M, Meehan S. 207.  et al. 2012. Molecular mechanisms used by chaperones to reduce the toxicity of aberrant protein oligomers. PNAS 109:12479–84 [Google Scholar]
  208. Cascella R, Conti S, Mannini B, Li X, Buxbaum JN. 208.  et al. 2013. Transthyretin suppresses the toxicity of oligomers formed by misfolded proteins in vitro. Biochim. Biophys. Acta 1832:2302–14 [Google Scholar]
  209. Mannini B, Mulvihill E, Sgromo C, Cascella R, Khodarahmi R. 209.  et al. 2014. Toxicity of protein oligomers is rationalized by a function combining size and surface hydrophobicity. ACS Chem. Biol. 9:2309–17 [Google Scholar]
  210. van Rooijen BD, Claessens MM, Subramaniam V. 210.  2010. Membrane permeabilization by oligomeric α-synuclein: in search of the mechanism. PLOS ONE 5:e14292 [Google Scholar]
  211. Oropesa-Nuñez R, Seghezza S, Dante S, Diaspro A, Cascella R. 211.  et al. 2016. Interaction of toxic and non-toxic HypF-N oligomers with lipid bilayers investigated at high resolution with atomic force microscopy. Oncotarget 7:44991–5004 [Google Scholar]
  212. Kayed R, Sokolov Y, Edmonds B, McIntire TM, Milton SC. 212.  et al. 2004. Permeabilization of lipid bilayers is a common conformation-dependent activity of soluble amyloid oligomers in protein misfolding diseases. J. Biol. Chem. 279:46363–66 [Google Scholar]
  213. Cremades N, Chen SW, Dobson CM. 213.  2017. Structure characteristics of α-synuclein oligomers. Int. Rev. Cell Mol. Biol. 329:79–143 [Google Scholar]
  214. Stöckl MT, Zijlstra N, Subramaniam V. 214.  2013. α-Synuclein oligomers: an amyloid pore? Insights into mechanisms of α-synuclein oligomer-lipid interactions. Mol. Neurobiol. 47:613–21 [Google Scholar]
  215. Brehme M, Voisine C, Rolland T, Wachi S, Soper JH. 215.  et al. 2014. A chaperome subnetwork safeguards proteostasis in aging and neurodegenerative disease. Cell Rep 9:1135–50 [Google Scholar]
  216. Nillegoda NB, Kirstein J, Szlachcic A, Berynskyy M, Stank A. 216.  et al. 2015. Crucial HSP70 co-chaperone complex unlocks metazoan protein disaggregation. Nature 524:247–51 [Google Scholar]
  217. Beeg M, Stravalaci M, Romeo M, Carrá AD, Cagnotto A. 217.  et al. 2016. Clusterin binds to Aβ1–42 oligomers with high affinity and interferes with peptide aggregation by inhibiting primary and secondary nucleation. J. Biol. Chem. 291:6958–66 [Google Scholar]
  218. Fernandez-Funez P, Sanchez-Garcia J, de Mena L, Zhang Y, Levites Y. 218.  et al. 2016. Holdase activity of secreted Hsp70 masks amyloid-β42 neurotoxicity in Drosophila. PNAS 113:E5212–21 [Google Scholar]
  219. Monsellier E, Chiti F. 219.  2007. Prevention of amyloid-like aggregation as a driving force of protein evolution. EMBO Rep 8:737–42 [Google Scholar]
  220. Tartaglia GG, Vendruscolo M. 220.  2009. Correlation between mRNA expression levels and protein aggregation propensities in subcellular localisations. Mol. Biosyst. 5:1873–76 [Google Scholar]
  221. De Baets G, Reumers J, Delgado Blanco J, Dopazo J, Schymkowitz J, Rousseau F. 221.  2011. An evolutionary trade-off between protein turnover rate and protein aggregation favors a higher aggregation propensity in fast degrading proteins. PLOS Comput. Biol. 7:e1002090 [Google Scholar]
  222. Singh S, Trikha S, Bhowmick DC, Sarkar AA, Jeremic AM. 222.  2015. Role of cholesterol and phospholipids in amylin misfolding, aggregation and etiology of islet amyloidosis. Adv. Exp. Med. Biol 85595–116 [Google Scholar]
  223. Hinton DR, Polk RK, Linse KD, Weiss MH, Kovacs K, Garner JA. 223.  1997. Characterization of spherical amyloid protein from a prolactin-producing pituitary adenoma. Acta Neuropathol 93:43–49 [Google Scholar]
  224. Benditt EP, Eriksen N. 224.  1971. Chemical classes of amyloid substance. Am. J. Pathol. 65:231–52 [Google Scholar]
  225. McKinnon C, Tabrizi SJ. 225.  2014. The ubiquitin-proteasome system in neurodegeneration. Antioxid. Redox Signal. 21:2302–21 [Google Scholar]
  226. Martinez-Lopez N, Athonvarangkul D, Singh R. 226.  2015. Autophagy and aging. Adv. Exp. Med. Biol 84773–87 [Google Scholar]
  227. Tartaglia GG, Pechmann S, Dobson CM, Vendruscolo M. 227.  2007. Life on the edge: a link between gene expression levels and aggregation rates of human proteins. Trends Biochem. Sci. 32:204–6 [Google Scholar]
  228. Ciryam P, Tartaglia GG, Morimoto RI, Dobson CM, Vendruscolo M. 228.  2013. Widespread aggregation and neurodegenerative diseases are associated with supersaturated proteins. Cell Rep 5:781–90 [Google Scholar]
  229. Freer R, Sormanni P, Vecchi G, Ciryam P, Dobson CM, Vendruscolo M. 229.  2016. A protein homeostasis signature in healthy brains recapitulates tissue vulnerability to Alzheimer's disease. Sci. Adv. 2:e1600947 [Google Scholar]
  230. Ciryam P, Kundra R, Freer R, Morimoto RI, Dobson CM, Vendruscolo M. 230.  2016. A transcriptional signature of Alzheimer's disease is associated with a metastable subproteome at risk for aggregation. PNAS 113:4753–58 [Google Scholar]
  231. Briggs R, Kennelly SP, O'Neill D. 231.  2016. Drug treatments in Alzheimer's disease. Clin. Med. 16:247–53 [Google Scholar]
  232. Valera E, Masliah E. 232.  2016. Therapeutic approaches in Parkinson's disease and related disorders. J. Neurochem. 139:346–52 [Google Scholar]
  233. Nuvolone M, Merlini G. 233.  2017. Systemic amyloidosis: novel therapies and role of biomarkers. Nephrol. Dial. Transplant. 32:770–80 [Google Scholar]
  234. Coelho T, Merlini G, Bulawa CE, Fleming JA, Judge DP. 234.  et al. 2016. Mechanism of action and clinical application of tafamidis in hereditary transthyretin amyloidosis. Neurol. Ther. 5:1–25 [Google Scholar]
  235. Habchi J, Chia S, Limbocker R, Mannini B, Ahn M. 235.  et al. 2017. Systematic development of small molecules to inhibit specific microscopic steps of Aβ42 aggregation in Alzheimer's disease. PNAS 114:E200–8 [Google Scholar]
  236. Ivanova MI, Sievers SA, Sawaya MR, Wall JS, Eisenberg D. 236.  2009. Molecular basis for insulin fibril assembly. PNAS 106:18990–95 [Google Scholar]
  237. Török M, Milton S, Kayed R, Wu P, McIntire T. 237.  et al. 2002. Structural and dynamic features of Alzheimer's Aβ peptide in amyloid fibrils studied by site-directed spin labeling. J. Biol. Chem. 277:40810–15 [Google Scholar]
  238. Lührs T, Ritter C, Adrian M, Riek-Loher D, Bohrmann B. 238.  et al. 2005. 3D structure of Alzheimer's amyloid-β(1-42) fibrils. PNAS 102:17342–47 [Google Scholar]
  239. Kheterpal I, Chen M, Cook KD, Wetzel R. 239.  2006. Structural differences in Aβ amyloid protofibrils and fibrils mapped by hydrogen exchange–mass spectrometry with on-line proteolytic fragmentation. J. Mol. Biol. 361:785–95 [Google Scholar]
  240. Miake H, Mizusawa H, Iwatsubo T, Hasegawa M. 240.  2002. Biochemical characterization of the core structure of α-synuclein filaments. J. Biol. Chem. 277:19213–19 [Google Scholar]
  241. Del Mar C, Greenbaum EA, Mayne L, Englander SW, Woods VL Jr. 241.  2005. Structure and properties of α-synuclein and other amyloids determined at the amino acid level. PNAS 102:15477–82 [Google Scholar]
  242. Kajava AV, Aebi U, Steven AC. 242.  2005. The parallel superpleated β-structure as a model for amyloid fibrils of human amylin. J. Mol. Biol. 348:247–52 [Google Scholar]
  243. Alexandrescu AT. 243.  2013. Amide proton solvent protection in amylin fibrils probed by quenched hydrogen exchange NMR. PLOS ONE 8:e56467 [Google Scholar]
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