The amyloid state and its association with protein misfolding diseases (original) (raw)

• Dobson, C. M. Protein folding and misfolding. Nature 426, 884–890 (2003).
  Article CAS PubMed Google Scholar
• Hardy, J. & Selkoe, D. J. Medicine - the amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297, 353–356 (2002).
  Article CAS PubMed Google Scholar
• Balch, W. E., Morimoto, R. I., Dillin, A. & Kelly, J. W. Adapting proteostasis for disease intervention. Science 319, 916–919 (2008). Provides a comprehensive overview of protein homeostasis and of the opportunities for therapeutic intervention that it offers.
  Article CAS PubMed Google Scholar
• Tanaka, M., Collins, S. R., Toyama, B. H. & Weissman, J. S. The physical basis of how prion conformations determine strain phenotypes. Nature 442, 585–589 (2006).
  Article CAS PubMed Google Scholar
• Chiti, F. & Dobson, C. M. Protein misfolding, functional amyloid, and human disease. Annu. Rev. Bioch. 75, 333–366 (2006).
  Article CAS Google Scholar
• Knowles, T. P. J. & Buehler, M. J. Nanomechanics of functional and pathological amyloid materials. Nature Nanotech. 6, 469–479 (2011).
  Article CAS Google Scholar
• Haass, C. & Selkoe, D. J. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nature Rev. Mol. Cell. Biol. 8, 101–112 (2007).
  Article CAS Google Scholar
• Eisenberg, D. & Jucker, M. The amyloid state of proteins in human diseases. Cell 148, 1188–1203 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Ballard, C. et al. Alzheimer's disease. Lancet 377, 1019–1031 (2011).
  Article PubMed Google Scholar
• Querfurth, H. W. & LaFerla, F. M. Mechanisms of disease Alzheimer's disease. N. Engl. J. Med. 362, 329–344 (2010).
  Article CAS PubMed Google Scholar
• Kim, Y. E., Hipp, M. S., Bracher, A., Hayer-Hartl, M. & Ulrich Hartl, F. Molecular chaperone functions in protein folding and proteostasis. Annu. Rev. Bioch. 82, 323–355 (2013).
  Article CAS Google Scholar
• Alzheimer's disease international. World Alzheimer report (2010).
• Dementia: A public health priority. World health organization and Alzheimer's disease international (2012).
• Olshansky, S. J. et al. A potential decline in life expectancy in the united states in the 21st century. N. Engl. J. Med. 352, 1138–1145 (2005).
  Article CAS PubMed Google Scholar
• Alzheimer's disease: Facts and figures. Alzheimer's association (2012).
• Walsh, D. M. et al. Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416, 535–539 (2002).
  Article CAS PubMed Google Scholar
• Cremades, N. et al. Direct observation of the interconversion of normal and toxic forms of α-synuclein. Cell 149, 1048–1059 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Cohen, S. I. A. et al. Proliferation of amyloid-β 42 aggregates occurs through a secondary nucleation mechanism. Proc. Natl Acad. Sci. USA 110, 9758–9763 (2013). Shows how the rapid proliferation of amyloid aggregates can be catalysed by the surfaces of existing amyloid fibrils.
  Article CAS PubMed Google Scholar
• Lesne, S. et al. A specific amyloid-β protein assembly in the brain impairs memory. Nature 440, 352–357 (2006).
  Article CAS PubMed Google Scholar
• Campioni, S. et al. A causative link between the structure of aberrant protein oligomers and their toxicity. Nature Chem. Biol. 6, 140–147 (2010).
  Article CAS Google Scholar
• Bucciantini, M. et al. Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases. Nature 416, 507–511 (2002).
  Article CAS PubMed Google Scholar
• Caughey, B. & Lansbury, P. T. Protofibrils, pores, fibrils, and neurodegeneration: Separating the responsible protein aggregates from the innocent bystanders. Annu. Rev. Neurosci. 26, 267–298 (2003).
  Article CAS PubMed Google Scholar
• Billings, L. M., Oddo, S., Green, K. N., McGaugh, J. L. & LaFerla, F. M. Intraneuronal a β causes the onset of early Alzheimer's disease-related cognitive deficits in transgenic mice. Neuron 45, 675–688 (2005).
  Article CAS PubMed Google Scholar
• Winner, B. et al. In vivo demonstration that α-synuclein oligomers are toxic. Proc. Natl Acad. Sci. USA 108, 4194–4199 (2011).
  Article CAS PubMed Google Scholar
• Koffie, R. M. et al. Oligomeric amyloid β associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques. Proc. Natl Acad. Sci. USA 106, 4012–4017 (2009).
  Article CAS PubMed Google Scholar
• Dobson, C. M. Protein misfolding, evolution and disease. Trends Bioch. Sci. 24, 329–332 (1999).
  Article CAS Google Scholar
• Greenwald, J. & Riek, R. On the possible amyloid origin of protein folds. J. Mol. Biol. 421, 417–426 (2012).
  Article CAS PubMed Google Scholar
• Carny, O. & Gazit, E. A model for the role of short self-assembled peptides in the very early stages of the origin of life. FASEB J. 19, 1051–1055 (2005).
  Article CAS PubMed Google Scholar
• DePas, W. H. & Chapman, M. R. Microbial manipulation of the amyloid fold. Res. Microbiol. 163, 592–606 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Fowler, D. M., Koulov, A. V., Balch, W. E. & Kelly, J. W. Functional amyloid - from bacteria to humans. Trends Bioch. Sci. 32, 217–224 (2007).
  Article CAS Google Scholar
• Fandrich, M. & Dobson, C. M. The behaviour of polyamino acids reveals an inverse side chain effect in amyloid structure formation. EMBO J. 21, 5682–5690 (2002).
  Article PubMed PubMed Central Google Scholar
• Knowles, T. P. J. et al. Observation of spatial propagation of amyloid assembly from single nuclei. Proc. Natl Acad. Sci. USA 108, 14746–14751 (2011).
  Article CAS PubMed Google Scholar
• Astbury, W. T., Dickinson, S. & Bailey, K. The X-ray interpretation of denaturation and the structure of the seed globulins. Biochem. J. 29, 2351–2360 (1935).
  Article CAS PubMed PubMed Central Google Scholar
• Kendrew, J. C. et al. 3-dimensional model of the myoglobin molecule obtained by X-ray analysis. Nature 181, 662–666 (1958).
  Article CAS PubMed Google Scholar
• Berman, H. M. et al. The protein data bank. Nucl. Acids Res. 28, 235–242 (2000).
  Article CAS PubMed Google Scholar
• Rosenbaum, D. M., Rasmussen, S. G. F. & Kobilka, B. K. The structure and function of g-protein-coupled receptors. Nature 459, 356–363 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Anfinsen, C. B. Principles that govern folding of protein chains. Science 181, 223–230 (1973).
  Article CAS PubMed Google Scholar
• Dill, K. A. & Chan, H. S. From Levinthal to pathways to funnels. Nature Struct. Biol. 4, 10–19 (1997).
  Article CAS PubMed Google Scholar
• Onuchic, J. N., Luthey-Schulten, Z. & Wolynes, P. G. Theory of protein folding: the energy landscape perspective. Annu. Rev. Phys. Chem. 48, 545–600 (1997).
  Article CAS PubMed Google Scholar
• Dobson, C. M., Sali, A. & Karplus, M. Protein folding: a perspective from theory and experiment. Angew. Chem. Int. Ed. 37, 868–893 (1998).
  Article Google Scholar
• Baldwin, A. J. et al. Metastability of native proteins and the phenomenon of amyloid formation. J. Am. Chem. Soc. 133, 14160–14163 (2011). Demonstrates that native states of proteins are intrinsically metastable against aggregation.
  Article CAS PubMed Google Scholar
• Gazit, E. The “correctly folded” state of proteins: is it a metastable state. Angew. Chem. Int. Ed. 41, 257–259 (2002).
  Article CAS Google Scholar
• Vendruscolo, M., Knowles, T. P. J. & Dobson, C. M. Protein solubility and protein homeostasis: A generic view of protein misfolding disorders. Cold Spring Harb. Perspect. Biol. 3, a010454 (2011).
  Article PubMed PubMed Central Google Scholar
• Wolff, S., Weissman, J. S. & Dillin, A. Differential scales of protein quality control. Cell 157, 52–64 (2014).
  Article CAS PubMed Google Scholar
• Dyson, H. J. & Wright, P. E. Intrinsically unstructured proteins and their functions. Nature Rev. Mol. Cell Biol. 6, 197–208 (2005).
  Article CAS Google Scholar
• Uversky, V. N. & Dunker, A. K. Understanding protein non-folding. Biochim. Biophys. Acta 1804, 1231–1264 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Dedmon, M. M., Lindorff-Larsen, K., Christodoulou, J., Vendruscolo, M. & Dobson, C. M. Mapping long-range interactions in α-synuclein using spin-label NMR and ensemble molecular dynamics simulations. J. Am. Chem. Soc. 127, 476–477 (2005).
  Article CAS PubMed Google Scholar
• Hou, L. M. et al. Solution NMR studies of the Aβ(1-40) and Aβ(1-42) peptides establish that the Met35 oxidation state affects the mechanism of amyloid formation. J. Am. Chem. Soc. 126, 1992–2005 (2004).
  Article CAS PubMed Google Scholar
• Varadi, M. et al. pE-DB: A database of structural ensembles of intrinsically disordered and of unfolded proteins. Nucl. Acids Res. 42, D326–D335 (2014).
  Article CAS PubMed Google Scholar
• Tartaglia, G. G. et al. Prediction of aggregation-prone regions in structured proteins. J. Mol. Biol. 380, 425–436 (2008).
  Article CAS PubMed Google Scholar
• Polymeropoulos, M. H. et al. Mutation in the α-synuclein gene identified in families with Parkinson's disease. Science 276, 2045–2047 (1997).
  Article CAS PubMed Google Scholar
• Spillantini, M. G. et al. α-synuclein in Lewy bodies. Nature 388, 839–840 (1997).
  Article CAS PubMed Google Scholar
• Westermark, P. et al. Amyloid fibrils in human insulinoma and islets of langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells. Proc. Natl Acad. Sci. USA 84, 3881–3885 (1987).
  Article CAS PubMed Google Scholar
• Waudby, C. A., Launay, H., Cabrita, L. D. & Christodoulou, J. Protein folding on the ribosome studied using NMR spectroscopy. Prog. Nucl. Magn. Reson. Spectrosc. 74, 57–75 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Chiti, F. & Dobson, C. M. Amyloid formation by globular proteins under native conditions. Nature Chem. Biol. 5, 15–22 (2009).
  Article CAS Google Scholar
• Kelly, J. W. The alternative conformations of amyloidogenic proteins and their multi-step assembly pathways. Curr. Opin. Struct. Biol. 8, 101–106 (1998).
  Article CAS PubMed Google Scholar
• Vendruscolo, M. & Dobson, C. M. Structural biology: protein self-assembly intermediates. Nature Chem. Biol. 9, 216–217 (2013).
  Article CAS Google Scholar
• Neupert, W. & Herrmann, J. M. Translocation of proteins into mitochondria. Annu. Rev. Bioch. 76, 723–749 (2007).
  Article CAS Google Scholar
• Chacinska, A., Koehler, C. M., Milenkovic, D., Lithgow, T. & Pfanner, N. Importing mitochondrial proteins: machineries and mechanisms. Cell 138, 628–644 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Meinema, A. C. et al. Long unfolded linkers facilitate membrane protein import through the nuclear pore complex. Science 333, 90–93 (2011).
  Article CAS PubMed Google Scholar
• Park, S. H. et al. PolyQ proteins interfere with nuclear degradation of cytosolic proteins by sequestering the Sis1p chaperone. Cell 154, 134–145 (2013).
  Article CAS PubMed Google Scholar
• Fletcher, D. A. & Mullins, D. Cell mechanics and the cytoskeleton. Nature 463, 485–492 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Omenetto, F. G. & Kaplan, D. L. New opportunities for an ancient material. Science 329, 528–531 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Anderson, V. J. & Lekkerkerker, H. N. W. Insights into phase transition kinetics from colloid science. Nature 416, 811–815 (2002).
  Article CAS PubMed Google Scholar
• Prusiner, S. B. Prions. Proc. Natl Acad. Sci. USA 95, 13363–13383 (1998).
  Article CAS PubMed Google Scholar
• Serio, T. R. et al. Nucleated conformational conversion and the replication of conformational information by a prion determinant. Science 289, 1317–1321 (2000).
  Article CAS PubMed Google Scholar
• Sipe, J. D. & Cohen, A. S. Review: History of the amyloid fibril. J. Struct. Biol. 130, 88–98 (2000).
  Article CAS PubMed Google Scholar
• Buxbaum, J. N. & Linke, R. P. A molecular history of the amyloidoses. J. Mol. Biol. 421, 142–159 (2012).
  Article CAS PubMed Google Scholar
• Stefani, M. & Dobson, C. M. Protein aggregation and aggregate toxicity: new insights into protein folding, misfolding diseases and biological evolution. J. Mol. Med. 81, 678–699 (2003).
  Article CAS PubMed Google Scholar
• Liao, L. et al. Proteomic characterization of postmortem amyloid plaques isolated by laser capture microdissection. J. Biol. Chem. 279, 37061–37068 (2004).
  Article CAS PubMed Google Scholar
• Wang, Q. et al. Proteomic analysis of neurofibrillary tangles in Alzheimer disease identifies GAPDH as a detergent-insoluble paired helical filament tau binding protein. FASEB J. 19, 869–871 (2005).
  Article CAS PubMed Google Scholar
• Xia, Q. et al. Proteomic identification of novel proteins associated with lewy bodies. Front. Biosci. 13, 3850–3856 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Sunde, M. et al. Common core structure of amyloid fibrils by synchrotron X-ray diffraction. J. Mol. Biol. 273, 729–739 (1997).
  Article CAS PubMed Google Scholar
• Sawaya, M. R. et al. Atomic structures of amyloid cross-β spines reveal varied steric zippers. Nature 447, 453–457 (2007).
  Article CAS PubMed Google Scholar
• Fitzpatrick, A. W. P. et al. Atomic structure and hierarchical assembly of a cross-β amyloid fibril. Proc. Natl Acad. Sci. USA 110, 5468–5473 (2013).
  Article CAS PubMed Google Scholar
• Petkova, A. T. et al. A structural model for Alzheimer's β-amyloid fibrils based on experimental constraints from solid state NMR. Proc. Natl Acad. Sci. USA 99, 16742–16747 (2002).
  Article CAS PubMed Google Scholar
• Wasmer, C. et al. Amyloid fibrils of the HET-s(218-289) prion form a β solenoid with a triangular hydrophobic core. Science 319, 1523–1526 (2008).
  Article CAS PubMed Google Scholar
• Luhrs, T. et al. 3D structure of Alzheimer's amyloid-β(1-42) fibrils. Proc. Natl Acad. Sci. USA 102, 17342–17347 (2005).
  Article CAS PubMed Google Scholar
• Guijarro, J. I., Sunde, M., Jones, J. A., Campbell, I. D. & Dobson, C. M. Amyloid fibril formation by an SH3 domain. Proc. Natl Acad. Sci. USA 95, 4224–4228 (1998).
  Article CAS PubMed Google Scholar
• Chiti, F. et al. Designing conditions for in vitro formation of amyloid protofilaments and fibrils. Proc. Natl Acad. Sci. USA 96, 3590–3594 (1999).
  Article CAS PubMed Google Scholar
• Urbanc, B. et al. In silico study of amyloid β-protein folding and oligomerization. Proc. Natl Acad. Sci. USA 101, 17345–17350 (2004).
  Article CAS PubMed Google Scholar
• Auer, S., Meersman, F., Dobson, C. M. & Vendruscolo, M. A generic mechanism of emergence of amyloid protofilaments from disordered oligomeric aggregates. PLoS Comp. Biol. 4, e1000222 (2008).
  Article CAS Google Scholar
• Tycko, R. Solid-state NMR studies of amyloid fibril structure. Annu. Rev. Phys. Chem. 62, 279–299 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Jimenez, J. L. et al. The protofilament structure of insulin amyloid fibrils. Proc. Natl Acad. Sci. USA 99, 9196–9201 (2002).
  Article CAS PubMed Google Scholar
• Sachse, C., Fandrich, M. & Grigorieff, N. Paired beta-sheet structure of an Aβ(1-40) amyloid fibril revealed by electron microscopy. Proc. Natl Acad. Sci. USA 105, 7462–7466 (2008).
  Article CAS PubMed Google Scholar
• Knowles, T. P. et al. Role of intermolecular forces in defining material properties of protein nanofibrils. Science 318, 1900–1903 (2007).
  Article CAS PubMed Google Scholar
• Krishnan, R. & Lindquist, S. L. Structural insights into a yeast prion illuminate nucleation and strain diversity. Nature 435, 765–772 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Collinge, J. & Clarke, A. R. A general model of prion strains and their pathogenicity. Science 318, 930–936 (2007).
  Article CAS PubMed Google Scholar
• Halfmann, R., Alberti, S. & Lindquist, S. Prions, protein homeostasis, and phenotypic diversity. Trends Cell Biol. 20, 125–133 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Wright, C. F., Teichmann, S. A., Clarke, J. & Dobson, C. M. The importance of sequence diversity in the aggregation and evolution of proteins. Nature 438, 878–881 (2005).
  Article CAS PubMed Google Scholar
• Knowles, T. P. J. et al. Twisting transition between crystalline and fibrillar phases of aggregated peptides. Phys. Rev. Lett. 109, 158101 (2012).
  Article CAS PubMed Google Scholar
• Smith, J. F., Knowles, T. P. J., Dobson, C. M., MacPhee, C. E. & Welland, M. E. Characterization of the nanoscale properties of individual amyloid fibrils. Proc. Natl Acad. Sci. USA 103, 15806–15811 (2006).
  Article CAS PubMed Google Scholar
• Tartaglia, G. G., Pechmann, S., Dobson, C. M. & Vendruscolo, M. Life on the edge: a link between gene expression levels and aggregation rates of human proteins. Trends Bioch. Sci. 32, 204–206 (2007).
  Article CAS Google Scholar
• Apetri, M. M., Maiti, N. C., Zagorski, M. G., Carey, P. R. & Anderson, V. E. Secondary structure of α -synuclein oligomers: characterization by Raman and atomic force microscopy. J. Mol. Biol. 355, 63–71 (2006).
  Article CAS PubMed Google Scholar
• Nettleton, E. J. et al. Characterization of the oligomeric states of insulin in self-assembly and amyloid fibril formation by mass spectrometry. Bioph. J. 79, 1053–1065 (2000).
  Article CAS Google Scholar
• Smith, D. P., Radford, S. E. & Ashcroft, A. E. Elongated oligomers in β2-microglobulin amyloid assembly revealed by ion mobility spectrometry-mass spectrometry. Proc. Natl Acad. Sci. USA 107, 6794–6798 (2010).
  Article CAS PubMed Google Scholar
• Bernstein, S. L. et al. Amyloid-β protein oligomerization and the importance of tetramers and dodecamers in the aetiology of Alzheimer's disease. Nature Chem. 1, 326–331 (2009).
  Article CAS Google Scholar
• Narayan, P. et al. The extracellular chaperone clusterin sequesters oligomeric forms of the amyloid-β1–40 peptide. Nature Struct. Mol. Biol. 19, 79–83 (2012).
  Article CAS Google Scholar
• Cohen, S. I. A., Vendruscolo, M., Dobson, C. M. & Knowles, T. P. J. From macroscopic measurements to microscopic mechanisms of protein aggregation. J. Mol. Biol. 421, 160–171 (2012).
  Article CAS PubMed Google Scholar
• Knowles, T. P. J. et al. An analytical solution to the kinetics of breakable filament assembly. Science 326, 1533–1537 (2009). Presents an analytical solution to the kinetic equations that describe protein aggregation, thus providing an effective method to identify the roles of the individual microscopic processes underlying protein aggregation.
  Article CAS PubMed Google Scholar
• ten Wolde, P.R. & Frenkel, D. Enhancement of protein crystal nucleation by critical density fluctuations. Science 277, 1975–1978 (1997).
  Article CAS PubMed Google Scholar
• Nelson, R. et al. Structure of the cross-β spine of amyloid-like fibrils. Nature 435, 773–778 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Jucker, M. & Walker, L. C. Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders. Ann. Neurol. 70, 532–540 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Fandrich, M. Absolute correlation between lag time and growth rate in the spontaneous formation of several amyloid-like aggregates and fibrils. J. Mol. Biol. 365, 1266–1270 (2007).
  Article CAS PubMed Google Scholar
• Collins, S. R., Douglass, A., Vale, R. D. & Weissman, J. S. Mechanism of prion propagation: amyloid growth occurs by monomer addition. PLoS Biol. 2, 1582–1590 (2004).
  Article CAS Google Scholar
• Bolognesi, B. et al. Single point mutations induce a switch in the molecular mechanism of the aggregation of the Alzheimer's disease associated Aβ42 peptide. ACS Chem. Biol. 9, 378–382 (2013).
  Article CAS PubMed Google Scholar
• Meier, M. et al. Plug-based microfluidics with defined surface chemistry to miniaturize and control aggregation of amyloidogenic peptides. Angew. Chem. Int. Ed. 121, 1515–1517 (2009).
  Article Google Scholar
• Lee, S. J., Desplats, P., Sigurdson, C., Tsigelny, I. & Masliah, E. Cell-to-cell transmission of non-prion protein aggregates. Nature Rev. Neurol. 6, 702–706 (2010).
  Article CAS Google Scholar
• Polymenidou, M. & Cleveland, D. W. The seeds of neurodegeneration: prion-like spreading in als. Cell 147, 498–508 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Cohen, S. et al. Spatial propagation of protein polymerization. Phys. Rev. Lett. 112, 098101 (2014).
  Article CAS PubMed Google Scholar
• Aguzzi, A. Cell biology: Beyond the prion principle. Nature 459, 924–925 (2009).
  Article CAS PubMed Google Scholar
• Aguzzi, A. & Rajendran, L. The transcellular spread of cytosolic amyloids, prions, and prionoids. Neuron 64, 783–790 (2009).
  Article CAS PubMed Google Scholar
• Jucker, M. & Walker, L. C. Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature 501, 45–51 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Walker, L. C., Diamond, M. I., Duff, K. E. & Hyman, B. T. Mechanisms of protein seeding in neurodegenerative diseases. JAMA Neurol. 70, 304–310 (2013).
  Article PubMed Google Scholar
• Maji, S. K. et al. Functional amyloids as natural storage of peptide hormones in pituitary secretory granules. Science 325, 328–332 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Chiti, F., Stefani, M., Taddei, N., Ramponi, G. & Dobson, C. M. Rationalization of the effects of mutations on peptide and protein aggregation rates. Nature 424, 805–808 (2003).
  Article CAS PubMed Google Scholar
• Dubay, K. F. et al. Prediction of the absolute aggregation rates of amyloidogenic polypeptide chains. J. Mol. Biol. 341, 1317–1326 (2004).
  Article CAS PubMed Google Scholar
• Fernandez-Escamilla, A. M., Rousseau, F., Schymkowitz, J. & Serrano, L. Prediction of sequence-dependent and mutational effects on the aggregation of peptides and proteins. Nature Biotech. 22, 1302–1306 (2004).
  Article CAS Google Scholar
• Pawar, A. P. et al. Prediction of “aggregation-prone” and “aggregation-susceptible” regions in proteins associated with neurodegenerative diseases. J. Mol. Biol. 350, 379–392 (2005).
  Article CAS PubMed Google Scholar
• Neudecker, P. et al. Structure of an intermediate state in protein folding and aggregation. Science 336, 362–366 (2012).
  Article CAS PubMed Google Scholar
• Broome, B. M. & Hecht, M. H. Nature disfavors sequences of alternating polar and non-polar amino acids: Implications for amyloidogenesis. J. Mol. Biol. 296, 961–968 (2000).
  Article CAS PubMed Google Scholar
• Richardson, J. S. & Richardson, D. C. Natural β-sheet proteins use negative design to avoid edge-to-edge aggregation. Proc. Natl Acad. Sci. USA 99, 2754–2759 (2002).
  Article CAS PubMed Google Scholar
• Otzen, D. E. & Oliveberg, M. Salt-induced detour through compact regions of the protein folding landscape. Proc. Natl Acad. Sci. USA 96, 11746–11751 (1999).
  Article CAS PubMed Google Scholar
• Kaganovich, D., Kopito, R. & Frydman, J. Misfolded proteins partition between two distinct quality control compartments. Nature 454, 1088–1095 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Tyedmers, J., Mogk, A. & Bukau, B. Cellular strategies for controlling protein aggregation. Nature Rev. Mol. Cell. Biol. 11, 777–788 (2010).
  Article CAS Google Scholar
• Bence, N. F., Sampat, R. M. & Kopito, R. R. Impairment of the ubiquitin-proteasome system by protein aggregation. Science 292, 1552–1555 (2001).
  Article CAS PubMed Google Scholar
• Ross, C. A. & Poirier, M. A. Protein aggregation and neurodegenerative disease. Nature Med. 10, S10–S17 (2004).
  Article CAS PubMed Google Scholar
• Glickman, M. H. & Ciechanover, A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol. Rev. 82, 373–428 (2002).
  Article CAS PubMed Google Scholar
• Rubinsztein, D. C. The roles of intracellular protein-degradation pathways in neurodegeneration. Nature 443, 780–786 (2006).
  Article CAS PubMed Google Scholar
• Webb, J. L., Ravikumar, B., Atkins, J., Skepper, J. N. & Rubinsztein, D. C. α-synuclein is degraded by both autophagy and the proteasome. J. Biol. Chem. 278, 25009–25013 (2003).
  Article CAS PubMed Google Scholar
• Mizushima, N., Levine, B., Cuervo, A. M. & Klionsky, D. J. Autophagy fights disease through cellular self-digestion. Nature 451, 1069–1075 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Morimoto, R. I. Regulation of the heat shock transcriptional response: Cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev. 12, 3788–3796 (1998).
  Article CAS PubMed Google Scholar
• Jiang, Q. et al. ApoE promotes the proteolytic degradation of Aβ. Neuron 58, 681–693 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Knowles, T. P. J. et al. Kinetics and thermodynamics of amyloid formation from direct measurements of fluctuations in fibril mass. Proc. Natl Acad. Sci. USA 104, 10016–10021 (2007).
  Article CAS PubMed Google Scholar
• Xu, L. Q. et al. Influence of specific Hsp70 domains on fibril formation of the yeast prion protein Ure2. Philos. Trans. R. Soc. B 368, 20110410 (2013).
  Article CAS Google Scholar
• Wilson, M. R. & Easterbrook-Smith, S. B. Clusterin is a secreted mammalian chaperone. Trends Bioch. Sci. 25, 95–98 (2000).
  Article CAS Google Scholar
• Harold, D. et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nature Genet. 41, 1088–1093 (2009).
  Article CAS PubMed Google Scholar
• Lambert, J.-C. et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nature Genet. 45, 1452–1458 (2013).
  Article CAS PubMed Google Scholar
• Lambert, J. C. et al. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. Nature Genet. 41, 1094–1099 (2009).
  Article CAS PubMed Google Scholar
• Tomic, J. L., Pensalfini, A., Head, E. & Glabe, C. G. Soluble fibrillar oligomer levels are elevated in Alzheimer's disease brain and correlate with cognitive dysfunction. Neurobiol. Dis. 35, 352–358 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Shankar, G. M. et al. Natural oligomers of the Alzheimer amyloid-β protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. J. Neurosci. 27, 2866–2875 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Palop, J. J. & Mucke, L. Amyloid-β-induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks. Nature Neurosci. 13, 812–818 (2010).
  Article CAS PubMed Google Scholar
• Feany, M. B. & Bender, W. W. A Drosophila model of Parkinson's disease. Nature 404, 394–398 (2000).
  Article CAS PubMed Google Scholar
• Luheshi, L. M., Crowther, D. C. & Dobson, C. M. Protein misfolding and disease: from the test tube to the organism. Curr. Opin. Chem. Biol. 12, 25–31 (2008).
  Article CAS PubMed Google Scholar
• Bilen, J. & Bonini, N. M. Drosophila as a model for human neurodegenerative disease. Annu. Rev. Genet. 39, 153–171 (2005).
  Article CAS PubMed Google Scholar
• Ben-Zvi, A., Miller, E. A. & Morimoto, R. I. Collapse of proteostasis represents an early molecular event in caenorhabditis elegans aging. Proc. Natl Acad. Sci. USA 106, 14914–14919 (2009).
  Article CAS PubMed Google Scholar
• Kaminksi Schierle, G. S. et al. In situ measurements of the formation and morphology of intracellular β-amyloid fibrils by super-resolution fluorescence imaging. J. Am. Chem. Soc. 133, 12902–12905 (2011).
  Article CAS Google Scholar
• McGuire, E. K. et al. Selenium-enhanced electron microscopic imaging of different aggregate forms of a segment of the amyloid beta peptide in cells. ACS Nano 6, 4740–4747 (2012).
  Article CAS PubMed Google Scholar
• Ries, J. et al. Superresolution imaging of amyloid fibrils with binding-activated probes. ACS Chem. Neurosci. 4, 1057–1061 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Lansbury, P. T. & Lashuel, H. A. A century-old debate on protein aggregation and neurodegeneration enters the clinic. Nature 443, 774–779 (2006).
  Article CAS PubMed Google Scholar
• Karran, E., Mercken, M. & De Strooper, B. The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics. Nature Rev. Drug Discov. 10, 698–712 (2011).
  Article CAS Google Scholar
• Lue, L. F. et al. Soluble amyloid β peptide concentration as a predictor of synaptic change in Alzheimer's disease. Am. J. Pathol. 155, 853–862 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Baglioni, S. et al. Prefibrillar amyloid aggregates could be generic toxins in higher organisms. J. Neurosci. 26, 8160–8167 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Cheon, M. et al. Structural reorganisation and potential toxicity of oligomeric species formed during the assembly of amyloid fibrils. PLoS Comp. Biol. 3, 1727–1738 (2007).
  Article CAS Google Scholar
• Bolognesi, B. et al. ANS binding reveals common features of cytotoxic amyloid species. ACS Chem. Biol. 5, 735–740 (2010).
  Article CAS PubMed Google Scholar
• Olzscha, H. et al. Amyloid-like aggregates sequester numerous metastable proteins with essential cellular functions. Cell 144, 67–78 (2011).
  Article CAS PubMed Google Scholar
• Narayan, P. et al. Single molecule characterization of the interactions between amyloid-β peptides and the membranes of hippocampal cells. J. Am. Chem. Soc. 135, 1491–1498 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Ciryam, P., Tartaglia, G. G., Morimoto, R. I., Dobson, C. M. & Vendruscolo, M. Widespread aggregation and neurodegenerative diseases are associated with supersaturated proteins. Cell Rep. 5, 781–790 (2013). Provides evidence that links protein supersaturation with ageing and neurodegeneration.
  Article CAS PubMed Google Scholar
• David, D. C. et al. Widespread protein aggregation as an inherent part of aging in C. elegans. PLoS Biol. 8, e1000450 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Gidalevitz, T., Ben-Zvi, A., Ho, K. H., Brignull, H. R. & Morimoto, R. I. Progressive disruption of cellular protein folding in models of polyglutamine diseases. Science 311, 1471–1474 (2006). This work demonstrates how protein homeostasis can be overwhelmed by the additional requests introduced by the presence of folding-defective proteins.
  Article CAS PubMed Google Scholar
• Koga, H., Kaushik, S. & Cuervo, A. M. Protein homeostasis and aging: the importance of exquisite quality control. Ageing Res. Rev. 10, 205–215 (2011).
  Article CAS PubMed Google Scholar
• Reis-Rodrigues, P. et al. Proteomic analysis of age-dependent changes in protein solubility identifies genes that modulate lifespan. Aging Cell 11, 120–127 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Cooper-Knock, J. et al. Gene expression profiling in human neurodegenerative disease. Nature Rev. Neurol. 8, 518–530 (2012).
  Article CAS Google Scholar
• Blalock, E. M. et al. Incipient Alzheimer's disease: microarray correlation analyses reveal major transcriptional and tumor suppressor responses. Proc. Natl Acad. Sci. USA 101, 2173–2178 (2004).
  Article CAS PubMed Google Scholar
• Dobson, M. The story of medicine (Quercus, 2013).
  Google Scholar
• Dobson, C. M. In the footsteps of alchemists. Science 304, 1259–1262 (2004).
  Article CAS PubMed Google Scholar
• Johnson, S. M. et al. Native state kinetic stabilization as a strategy to ameliorate protein misfolding diseases: a focus on the transthyretin amyloidoses. Acc. Chem. Res. 38, 911–921 (2005).
  Article CAS PubMed Google Scholar
• Razavi, H. et al. Benzoxazoles as transthyretin amyloid fibril inhibitors: synthesis, evaluation, and mechanism of action. Angew. Chem. Int. Ed. 42, 2758–2761 (2003). Provides initial evidence that stabilizing native states against aggregation offers effective therapeutic interventions.
  Article CAS Google Scholar
• Bulawa, C. E. et al. Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade. Proc. Natl Acad. Sci. USA 109, 9629–9634 (2012).
  Article CAS PubMed Google Scholar
• Uversky, V. N. Intrinsically disordered proteins and novel strategies for drug discovery. Expert Opin. Drug Discov. 7, 475–488 (2012).
  Article CAS PubMed Google Scholar
• Tóth, G. et al. Targeting the intrinsically disordered structural ensemble of α-synuclein by small molecules as a potential therapeutic strategy for Parkinson's disease. PLoS ONE 9, e87133 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Arosio, P., Vendruscolo, M., Dobson, C. M. & Knowles, T. P. Chemical kinetics for drug discovery to combat protein aggregation diseases. Trends Pharmacol. Sci. 35, 127–135 (2014).
  Article CAS PubMed Google Scholar
• Baigent, C. et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 366, 1267–1278 (2005).
  Article CAS PubMed Google Scholar
• Fersht, A. R. Structure and mechanism in protein science: A guide to enzyme catalysis and protein folding (W. H. Freeman, 1999).
  Google Scholar
• De Strooper, B., Vassar, R. & Golde, T. The secretases: enzymes with therapeutic potential in Alzheimer disease. Nature Rev. Neurol. 6, 99–107 (2010).
  Article CAS Google Scholar
• Dumoulin, M. & Dobson, C. M. Probing the origins, diagnosis and treatment of amyloid diseases using antibodies. Biochimie 86, 589–600 (2004).
  Article CAS PubMed Google Scholar
• Hard, T. & Lendel, C. Inhibition of amyloid formation. J. Mol. Biol. 421, 441–465 (2012).
  Article CAS PubMed Google Scholar
• Luheshi, L. M. et al. Sequestration of the Aβ peptide prevents toxicity and promotes degradation in vivo. PLoS Biol. 8, e1000334 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Schenk, D. Amyloid-β immunotherapy for Alzheimer's disease: The end of the beginning. Nature Rev. Neurosci. 3, 824–828 (2002).
  Article CAS Google Scholar
• Schenk, D., Basi, G. S. & Pangalos, M. N. Treatment strategies targeting amyloid β-protein. Cold Spring Harb. Perspect. Med. 2, a006387 (2012).
  Article CAS PubMed PubMed Central Google Scholar