Insights into Aβ aggregation: A molecular dynamics perspective

Current Topics in Medicinal Chemistry

Volumn 12, Issue 22, 2012, Pages 2596-2610

  Shea, Joan Emma ^a   Urbanc, Brigita ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b DREXEL UNIVERSITY   (United States)

Author keywords

Alzheimer amyloid ; Coarsegrained simulations; Peptide; Protein aggregation; Replica exchange molecular dynamics simulations

Indexed keywords

ALZHEIMER DISEASE; AMINO ACID SEQUENCE; AMYLOID BETA-PEPTIDES; HUMANS; MOLECULAR DYNAMICS SIMULATION; MOLECULAR SEQUENCE DATA; MUTATION; PROTEIN FOLDING; SOLVENTS;

EID: 84874874349     PISSN: 15680266     EISSN: 18734294     Source Type: Journal    
DOI: 10.2174/1568026611212220012     Document Type: Review

References (166)

1. Tanzi, R. E.; Gusella, J. F.; Watkins, P. C.; Bruns, G. A. B.; St. George-Hyslop, P. H.; Van Keuren, M. L.; Patterson, D.; Pagan, S.; Kurnit, D. M.; Neve, R. L. Amyloid β-protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. Science, 1987, 235, 880-884.
2. Hardy, J. A.; Higgins, G. A. Alzheimer's Disease: The Amyloid Cascade Hypothesis. Science, 1992, 256, 184-185.
3. Kirkitadze, M. D.; Bitan, G.; Teplow, D. B. Paradigm Shifts in Alzheimer's Disease and Other Neurodegenerative Disorders: The Emerging Role of Oligomeric Assemblies. J Neurosci Res, 2002, 69, 567-577.
4. Klein, W. L.; Stine, W. B.; Teplow, D. B. Small assemblies of unmodified amyloid β-protein are the proximate neurotoxin in Alzheimer's disease. Neurobiol Aging, 2004, 25, 569-580.
5. Hardy, J.; Selkoe, D. J. The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to Therapeutics. Science, 2002, 297, 353-356.
6. Hardy, J. The amyloid hypothesis for Alzheimer's disease: a critical reappraisal. J. Neurochem., 2009, 110, 1129-1134.
7. Kamino, K. et al. Linkage and mutational analysis of familial Alzheimer disease kindreds for the APP gene region. Am. J. Hum. Genet., 1992, 51, 998-1014.
8. Nilsberth, C.; Westlind-Danielsson, A.; Eckman, C. B.; Condron, M. M.; Axelman, K.; Forsell, C.; Stenh, C.; Luthman, J.; Teplow, D. B.; Younkin, S. G.; Naslund, J.; Lannfelt, L. The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Aβ protofibril formation. Nat Neurosci, 2001, 4, 887-893.
9. Paivio, A.; Jarvet, J.; Gräslund, A.; Lannfelt, L.; Westlind-Danielsson, A. Unique physic- ochemical profile of β-amyloid peptide variant Aβ1-40 E22G protofibrils: Conceivable neuropathogen in Arctic mutant carriers. J. Mol. Biol., 2004, 339, 145-59.
10. Whalen, B.; Selkoe, D.; Hartley, D. Small non-fibrillar assemblies of amyloid β-protein bearing the Arctic mutation induce rapid neuritic degeneration. Neurobiol. Dis., 2005, 20, 254-266.
11. Grabowski, T. J.; Cho, H. S.; Vonsattel, J. P. G.; Rebeck, G. W.; Greenberg, S. M. Novel amyloid precursor protein mutation in an Iowa family with dementia and severe cerebral amyloid angiopathy. Ann Neurol, 2001, 49, 697-705.
12. Van Nostrand, W.; Melchor, J.; Cho, H.; Greenberg, S.; Rebeck, G. Pathogenic effects of D23N Iowa mutant amyloid β-protein. J. Biol. Chem., 2001, 276, 32860-32866.
13. Levy, E.; Carman, M. D.; Fernandez-Madrid, I. J.; Power, M. D.; Lieberburg, I.; van Duinen, S. G.; Bots, G. T. A. M.; Luyendijk, W.; Frangione, B. Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch-type. Science, 1990, 248, 1124-1126.
14. Tomidokoro, Y.; Rostagno, A.; Neubert, T. A.; Lu, Y.; Rebeck, G.; Frangione, B.; Greenberg, S.; Ghiso, J. Iowa Variant of Familial Alzheimer's Disease - Accumulation of Post-translationally Modified AβD23N in Parenchymal and Cerebrovascular Amyloid Deposits. Am. J. Pathol., 2010, 176, 1841-1854.
15. Walsh, D. M.; Lomakin, A.; Benedek, G. B.; Condron, M. M.; Teplow, D. B. Amyloid β-protein fibrillogenesis. Detection of a protofibrillar intermediate. J Biol Chem, 1997, 272, 22364-22372.
16. Murakami, K.; Irie, K.; Morimoto, A.; Ohigashi, H.; Shindo, M.; Nagao, M.; Shimizu, T.; Shirasawa, T. Neurotoxicity and Physicochemical Properties of Aβ Mutant Peptide From Cerebral Amyloid Angiopathy - Implication For the Pathogenesis of Cerebral Amyloid Angiopathy and Alzheimer's Disease. J. Biolog. Chem., 2003, 278, 46179-46187.
17. Mitsutake, A.; Sugita, Y.; Okamoto, Y. Generalized-ensemble algorithms for molecular simulations of biopolymers. Biopolymers, 2001, 60, 96-123.
18. Nymeyer, H.; Gnanakaran, S.; Garcia, A. E. Atomic simulations of protein folding, using the replica exchange algorithm. Methods. Enzymol., 2004, 383, 119-149.
19. Wu, C.; Shea, J. E. Coarse-grained models for protein aggregation. Curr. Opin. Struct. Biol., 2011, 21, 209-220.
20. Ding, F.; Borreguero, J. M.; Buldyrev, S. V.; Stanley, H. E.; Dokholyan, N. V. Mechanism for the α-Helix to β-Hairpin Transition. Proteins: Struc., Funct., and Genet., 2003, 53, 220-228.
21. Nguyen, H.; Hall, C. Molecular dynamics simulations of spontaneous fibril formation by random-coil peptides. Proc. Natl. Acad. Sci. USA., 2004, 101, 16180-16185.
22. Nguyen, H.; Hall, C. Phase diagrams describing fibrillization by polyalanine peptides. Biophys. J., 2004, 87, 4122-4134.
23. Nguyen, H.; Hall, C. Kinetics of fibril formation by polyalanine peptides. J. Biol. Chem., 2005, 280, 9074-9082.
24. Nguyen, H. D.; Hall, C. K. Spontaneous Fibril Formation by Polyalanines: Discontinuous Molecular Dynamics Simulations. J Am Chem Soc, 2006, 128, 1890-1901.
25. Urbanc, B.; Cruz, L.; Ding, F.; Sammond, D.; Khare, S.; Buldyrev, S. V.; Stanley, H. E.; Dokholyan, N. V. Molecular Dynamics Simulation of Amyloid β Dimer Formation. Biophys. J., 2004, 87, 2310-2321.
26. Bitan, G.; Kirkitadze, M. D.; Lomakin, A.; Vollers, S. S.; Benedek, G. B.; Teplow, D. B. Amyloid β-protein (Aβ) assembly: Aβ40 and Aβ42 oligomerize through distinct pathways. Proc. Natl. Acad. Sci. USA., 2003, 100, 330-335.
27. Urbanc, B.; Cruz, L.; Yun, S.; Buldyrev, S. V.; Bitan, G.; Teplow, D. B.; Stanley, H. E. In silico study of amyloid β-protein folding and oligomerization. Proc. Natl. Acad. Sci. USA., 2004, 101, 17345-17350.
28. Urbanc, B.; Borreguero, J. M.; Cruz, L.; Stanley, H. E. Aβ initio Discrete Molecular Dynamics Approach to Protein Folding and Aggregation. Methods. Enzymol., 2006, 412, 314-338.
29. Cheon, M.; Chang, I.; Hall, C. Extending the PRIME Model for Protein Aggregation to All, 20 Amino Acids. Proteins, 2010, 78, 2950-2960.
30. Cheon, M.; Chang, I.; Hall, C. Spontaneous Formation of Twisted Aβ(16-22) Fibrils inbLarge-Scale Molecular-Dynamics Simulations. Biophys. J., 2011, 101, 2493-2501.
31. Wagoner, V.; Cheon, M.; Chang, I.; Hall, C. Fibrillization propensity for short designed hexapeptides predicted by computer simulation. J. Mol. Biol., 2012, 416, 598-609.
32. Derreumaux, P.; Mousseau, N. Coarse-grained protein molecular dynamics simulations. J.Chem. Phys., 2007, 126, 025101.
33. Maupetit, J.; Tufféry, P.; Derreumaux, P. A coarse-grained protein force field for folding and structure prediction. Proteins, 2007, 69, 394-408.
34. Maupetit, J.; Derreumaux, P.; Tufféry, P. A fast method for largescale de novo peptide and miniprotein structure prediction. J. Comput. Chem., 2010, 31, 726-738.
35. Chebaro, Y.; Dong, X.; Laghaei, R.; Derreumaux, P.; Mousseau, N. Replica exchange molecular dynamics simulations of coarsegrained proteins in implicit solvent. J. Phys. Chem.B, 2009,113,267-274.
36. Laghaei, R.; Mousseau, N.; Wei, G. Effect of the Disulfide Bond on the Monomeric Structure of Human Amylin Studied by Combined Hamiltonian and Temperature Replica Exchange Molecular Dynamics Simulations. J. Phys. Chem. B, 2010, 114, 7071-7077.
37. Sugita, Y.; Okamoto, Y. Replica-exchange molecular dynamics method for protein folding. Chem. Phys. Lett., 1999, 314, 141-151.
38. Fukunishi, H.; Watanabe, O.; Takada, S. On the Hamiltonian replica exchange method for efficient sampling of biomolecular systems: Application to protein structure prediction. J. Chem. Phys., 2002, 116, 9058-9067.
39. Côté, S.; Laghaei, R.; Derreumaux, P.; Mousseau, N. Distinct Dimerization for Various Alloforms of the Amyloid-β Protein: Aβ(1- 40), Aβ(1-42), and Aβ(1-40)(D23N). J. Phys. Chem. B, 2012, 116, 4043-4055.
40. Thirumalai, D.; Klimov, D. K.; Dima, R. I. Emerging ideas on the molecular basis of protein and peptide aggregation. Curr. Opin. Struc. Biol., 2003, 13, 146-159.
41. Urbanc, B.; Cruz, L.; Teplow, D. B.; Stanley, H. E. Computer Simulations of Alzheimer's Amyloid β-Protein Folding and Assembly. Curr. Alzheimer Res., 2006, 3, 493-504.
42. Teplow, D. B.; Lazo, N. D.; Bitan, G.; Bernstein, S.; Wyttenbach, T.; Bowers, M. T.; Baumketner, A.; Shea, J.-E.; Urbanc, B.; Cruz, L.; Borreguero, J.; Stanley, H. E. Elucidating Amyloid β-Protein Folding and Assembly: A Multidisciplinary Approach. Acc. Chem. Res., 2006, 39, 635-645.
43. Wei, G.; Song, W.; Derreumaux, P.; Mousseau, N. Self-assembly of amyloid-forming peptides by molecular dynamics simulations. Front. Biosci., 2008, 13, 5681-5692.
44. Straub, J. E.; Thirumalai, D. Principles governing oligomer formation in amyloidogenic peptides. Curr. Opin. Struct. Biol., 2010, 20, 187-195.
45. Straub, J. E.; Thirumalai, D. Toward a Molecular Theory of Early and Late Events in Monomer to Amyloid Fibril Formation. Ann. Rev. Phys. Chem., 2011, 62, 437-463.
46. Baumketner, A.; Bernstein, S. L.; Wyttenbach, T.; Bitan, G.; Teplow, D. B.; Bowers, M. T.; Shea, J.-E. Amyloid β-protein monomer structure: A computational and experimental study. Protein Sci, 2006, 15, 420-428.
47. Yang, M.; Teplow, D. B. Amyloid β-Protein Monomer Folding: Free-Energy Surfaces Reveal Alloform-Specific Differences. J. Mol. Biol., 2008, 384, 450-464.
48. Kim, S.; Takeda, T.; Klimov, D. K. Mapping Conformational Ensembles of Aβ Oligomers in Molecular Dynamics Simulations. Biophys. J., 2010, 99, 1949-1958.
49. Wise Scira, O.; Xu, L.; Kitahara, T.; Perry, G.; Coskuner, O. Amyloid- β peptide structure in aqueous solution varies with fragment size. J. Chem. Phys., 2011, 135, 205101-1-205101-13.
50. Xu, Y.; Shen, J.; Luo, X.; Zhu, W.; Chen, K.; Ma, J.; Jiang, H. Conformational transition of amyloid β-peptide. Proc. Natl. Acad. Sci. USA., 2005, 102, 5403-5407.
51. Luttmann, E.; Fels, G. All-atom molecular dynamics studies of the full-length β-amyloid peptides. Chem. Phys., 2006, 323, 138-147.
52. Tomaselli, S.; Esposito, V.; Vangone, P.; van Nuland, N. A. J.; Bonvin, A. M. J. J.; Guerrini, R.; Tancredi, T.; Temussi, P. A.; Picone, D. The α-to-β conformational transition of Alzheimer's Aβ-(1-42) peptide in aqueous media is reversible: a step by step conformational analysis suggests the location of conformation seeding. Chembiochem, 2006, 7, 257-267.
53. Raffa, D. F.; Rauk, A. Molecular Dynamics Study of the Amyloid Peptide of Alzheimer's Disease and Its Divalent Copper Complexes. J. Phys. Chem. B, 2007, 111, 3789-3799.
54. Sgourakis, N.; Yan, Y.; McCallum, S.; Wang, C.; Garcia, A. The Alzheimer's Peptides Aβ40 and 42 Adopt Distinct Conformations in Water: A Combined MD/NMR Study. J. Mol. Biol., 2007, 368, 1448-1457.
55. Triguero, L.; Singh, R.; Prabhakar, R. Comparative Molecular Dynamics Studies of Wild- Type and Oxidized Forms of Full-Length Alzheimer Amyloid β-Peptides Aβ(1-40) and Aβ(1-42). J. Phys. Chem. B, 2008, 112, 7123-7131.
56. Yang, C.; Zhu, X.; Li, J.; Chen, K. Molecular dynamics simulation study on conformational behavior of Aβ(1-40) and Aβ (1-42) in water and methanol. J. Mol. Struc. - THEOCHEM, 2009, 907, 51-56.
57. Bora, R. P.; Prabhakar, R. Translational, rotational and internal dynamics of amyloid β-peptides (Aβ40 and Aβ42] from molecular dynamics simulations. J. Chem. Phys., 2009, 131, 155103.
58. Davis, C. H.; Berkowitz, M. L. Structure of the Amyloid-β(1-42) Monomer Absorbed to Model Phospholipid Bilayers: A Molecular Dynamics Study. Biophys. J., 2009, 96, 785-797.
59. Rubinstein, A.; Lyubchenko, Y. L.; Sherman, S. Dynamic properties of pH-dependent structural organization of the amyloidogenic β-protein (1-40). Prion, 2009, 3, 31-43.
60. Lee, C.; Ham, S. Characterizing Amyloid-Beta Protein Misfolding From Molecular Dynamics Simulations With Explicit Water. J. Comput. Chem., 2011, 32, 349-355.
61. Sgourakis, N.; Merced-Serrano, M.; Boutsidis, C.; Drineas, P.; Du, Z.; Wang, C.; Garcia, A. Atomic-Level Characterization of the Ensemble of the Aβ(1-42) Monomer in Water Using Unbiased Molecular Dynamics Simulations and Spectral Algorithms. J. Mol. Biol., 2011, 368, 1448-1457.
62. Velez-Vega, C.; Escobedo, F. Characterizing the Structural Behavior of Selected Aβ42 Monomers with Different Solubilities. J. Phys. Chem. B, 2011, 115, 4900-4910.
63. Ball, K. A.; Phillips, A. H.; Nerenberg, P. S.; Fawzi, N. L.; Wemmer, D. E.; Head Gordon, T. Homogeneous and Heterogeneous Tertiary Structure Ensembles of Amyloid-β Peptides. Biochemistry, 2011, 50, 7612-7628.
64. Lin, Y.-S.; Bowman, G. R.; Beauchamp, K. A.; Pande, V. S. Investigating How Peptide Length and a Pathogenic Mutation Modify the Structural Ensemble of Amyloid Beta Monomer. Biophys. J., 2012, 102, 315-324.
65. Barz, B.; Urbanc, B. Dimer Formation Enhances Structural Differences between Amyloid β-Protein (1-40) and (1-42): An Explicit-Solvent Molecular Dynamics Study. PLoS One, 2012, 7, e34345.
66. Yun, S.; Urbanc, B.; Cruz, L.; Bitan, G.; Teplow, D. B.; Stanley, H. E. Role of Electro-static Interactions in Amyloid β-protein (Aβ) Oligomer Formation: A Discrete Molecular Dynamics Study. Biophys J, 2007, 92, 4064-4077.
67. Lam, A.; Teplow, D. B.; Stanley, H. E.; Urbanc, B. Effects of the Arctic (E22βG) Mutation on Amyloid β-Protein Folding: Discrete Molecular Dynamics Study. J. Am. Chem. Soc., 2008, 130, 17413-17422.
68. Côté, S.; Derreumaux, P.; Mousseau, N. Distinct Morphologies for Amyloid Protein Monomer: Aβ1-40, Aβ1-42, and Aβ1-40(D23N). J. Chem. Theory Comput., 2011, 7, 2584-2592.
69. Samiotakis, A.; Homouz, D.; Cheung, M. Multiscale investigation of chemical interference in proteins. J. Chem. Phys., 2010, 132, 175101.
70. Coles, M.; Bicknell, W.; Watson, A. A.; Fairlie, D. P.; Craik, D. J. Solution Structure of Amyloid β-Peptide(1-40) in a Water-Micelle Environment. Is the Membrane-Spanning Domain Where We Think It Is? Biochemistry, 1998, 37, 11064-11077.
71. Crescenzi, O.; Tomaselli, S.; Guerrini, R.; Salvadori, S.; D'Ursi, A. M.; Temussi, P. A.; Picone, D. Solution structure of the Alzheimer amyloid β-peptide (1-42) in an apolar microenvironment: Similarity with a virus fusion domain. Eur J Biochem, 2002, 269, 5642-5648.
72. Zhang, S.; Iwata, K.; Lachenmann, M. J.; Peng, J. W.; Li, S.; Stimson, E. R.; Lu, Y.; Felix, A. M.; Maggio, J. E.; Lee, J. P. The Alzheimer's peptide Aβ adopts a collapsed coil structure in water. J Struct Biol, 2000, 130, 130-141.
73. Terzi, E.; Hölzemann, G.; Seelig, J. Self-association of β-amyloid peptide (1-40) in solution and binding to lipid membrane. J. Mol. Biol., 1995, 252, 633-642.
74. Terzi, E.; Hölzemann, G.; Seelig, J. Interaction of Alzheimer β- amyloid peptide (1-40) with lipid membranes. Biochemistry, 1997, 36, 14845-14852.
75. McLaurin, J.; Chakrabartty, A. Characterization of the interactions of Alzheimer's β- amyloid peptides with phospholipid membranes. Eur. J. Biochem., 1997, 245, 355-363.
76. Lazo, N. D.; Grant, M. A.; Condron, M. C.; Rigby, A. C.; Teplow, D. B. On the nucleation of amyloid β-protein monomer folding. Protein Sci, 2005, 14, 1581-1596.
77. Grant, M. A.; Lazo, N. D.; Lomakin, A.; Condron, M. M.; Arai, H.; Yamin, G.; Rigby, A. C.; Teplow, D. B. Familial Alzheimer's disease mutations alter the stability of the amyloid β-protein monomer folding nucleus. Proc. Natl. Acad. Sci. USA., 2007, 104, 16522-16527.
78. Fawzi, N.; Phillips, A.; Ruscio, J.; Doucleff, M.; Wemmer, D.; Head-Gordon, T. Structure and Dynamics of the Aβ[21-30] Peptide From the Interplay of NMR Experiments and Molecular Simulations. J. Am. Chem. Soc., 2008, 130, 6145-6158.
79. Murray, M.; Krone, M.; Bernstein, S.; Baumketner, A.; Condron, M.; Lazo, N.; Teplow, D.; Wyttenbach, T.; Shea, J.; Bowers, M. Amyloid β-Protein: Experiment and Theory on the 21-30 Fragment. J. Phys. Chem. B, 2009, 113, 6041-6046.
80. Roychaudhuri, R.; Yang, M.; Condron, M. M.; Teplow, D. B. Structural dynamics of the amyloid β-protein monomer folding nucleus. Biochemistry, 2012, 51, 3957-3959.
81. Borreguero, J. M.; Urbanc, B.; Lazo, N. D.; Buldyrev, S. V.; Teplow, D. B.; Stanley, H. E. Folding events in the 21-30 region of amyloid β-protein (Aβ) studied in silico. Proc. Natl. Acad. Sci. USA., 2005, 102, 6015-6020.
82. Cruz, L.; Urbanc, B.; Borreguero, J. M.; Lazo, N. D.; Teplow, D. B.; Stanley, H. E. Solvent and mutation effects on the nucleation of amyloid β-protein folding. Proc. Natl. Acad. Sci. USA., 2005, 102, 18258-18263.
83. Baumketner, A.; Bernstein, S. L.; Wyttenbach, T.; Lazo, N. D.; Teplow, D. B.; Bowers, M. T.; Shea, J.-E. Structure of the 21-30 fragment of amyloid β-protein. Protein Sci, 2006, 15, 1239-1247.
84. Chen, W.; Mousseau, N.; Derreumaux, P. The conformations of the amyloid-β [21-30] fragment can be described by three families in solution. J. Chem. Phys., 2006, 125, 084911.
85. Tarus, B.; Straub, J. E.; Thirumalai, D. Structures and Free-Energy Landscapes of the Wild Type and Mutants of the Aβ21-30 Peptide Are Determined by an Interplay between Intrapeptide Electrostatic and Hydrophobic Interactions. J. Mol. Biol., 2008, 379, 815-829.
86. Krone, M. G.; Baumketner, A.; Bernstein, S. L.; Wyttenbach, T.; Lazo, N. D.; Teplow, D. B.; Bowers, M. T.; Shea, J.-E. Effects of Familial Mutations on the Folding Nucleation of the Alzheimer Amyloid β-Protein. J. Mol. Biol., 2008, 381, 221-228.
87. Cruz, L.; Rao, J. S.; Teplow, D. B.; Urbanc, B. Dynamics of Metastable β-Hairpin Structures in the Folding Nucleus of Amyloid β-Protein. J. Phys. Chem. B, 2012, 116, 6311-6325.
88. Olubiyi, O.; Strodel, B. Structures of the Amyloid β-Peptides Aβ1-40 and Aβ1-42 as Influenced by pH and a D-Peptide. J. Phys. Chem. B, 2012, 116, 3280-3291.
89. Riek, R.; Güntert, P.; Döbeli, H.; Wipf, B.; Wüthrich, K. NMR studies in aqueous solution fail to identify significant conformational differences between the monomeric forms of two Alzheimer peptides with widely different plaque-competence, Aβ(1-40)ox and Aβ(1-42)ox. Eur J Biochem, 2001, 268, 5930-5936.
90. Murakami, K.; Irie, K.; Ohigashi, H.; Hara, H.; Nagao, M.; Shimizu, T.; Shirasawa, T. Formation and stabilization model of the 42-mer Aβ radical: implications for the long- lasting oxidative stress in Alzheimer's disease. J. Am. Chem. Soc., 2005, 127, 15168-15174.
91. Yan, Y.; Wang, C. Aβ42 is More Rigid Than Aβ40 at the C Terminus: Implications for Aβ Aggregation and Toxicity. J Mol Biol, 2006, 364, 853-862.
92. Lim, K. H.; Collver, H. H.; Le, Y. T.; Nagchowdhuri, P.; Kenney, J. M. Characterizations of distinct amyloidogenic conformations of the Aβ(1-40) and (1-42) peptides. Biochem Biophys Res Commun, 2007, 353, 443-449.
93. Takeda, T.; Klimov, D. Probing the Effect of Amino-Terminal Truncation for Aβ1-40 Peptides. J. Phys. Chem. B, 2009, 113, 6692-6702.
94. Ono, K.; Condron, M. M.; Teplow, D. B. Structure-neurotoxicity relationships of amyloid β-protein oligomers. Proc. Natl. Acad. Sci. USA., 2009, 106, 14745-14750.
95. Urbanc, B.; Betnel, M.; Cruz, L.; Bitan, G.; Teplow, D. B. Elucidation of Amyloid β-Protein Oligomerization Mechanisms: Discrete Molecular Dynamics Study. J. Am. Chem. Soc., 2010, 132, 4266-4280.
96. Bernstein, S. L.; Dupuis, N. F.; Lazo, N. D.; Wyttenbach, T.; Condron, M. M.; Bitan, G.; Teplow, D. B.; Shea, J.-E.; Ruotolo, B. T.; Robinson, C. V.; Bowers, M. T. Amyloid-β protein oligomerization and the importance of tetramers and dodecamers in the aetiology of Alzheimer's disease. Nat. Chem., 2009, 1, 326-331.
97. Szabo, P.; Relkin, N.; Weksler, M. Natural human antibodies to amyloid beta peptide. Autoimmun. Rev., 2008, 7, 415-420.
98. Esler, W. P.; Stimson, E. R.; Jennings, J. M.; Vinters, H. V.; Ghilardi, J. R.; Lee, J. P.; Mantyh, P. W.; Maggio, J. E. Alzheimer's Disease Amyloid Propagation by a Template- Dependent Dock-Lock Mechanism. Biochemistry, 2000, 39, 6288-6295.
99. Glabe, C. G. Conformation-dependent antibodies target diseases of protein misfolding. Trends in Biochem Sci, 2004, 29, 542-547.
100. Necula, M.; Kayed, R.; Milton, S.; Glabe, C. Small Molecule Inhibitors of Aggregation Indicate That Amyloid β Oligomerization and Fibrillization Pathways Are Independent And Distinct. J. Biol. Chem., 2007, 282, 10311-10324.
101. Bitan, G.; Lomakin, A.; Teplow, D. B. Amyloidn β- Proteinn Oligomerization: Prenucleation Interactions Revealed by Photo-Induced Cross-linking of Unmodified Proteins. J. Biol. Chem., 2001, 276, 35176-35184.
102. Bitan, G.; Vollers, S. S.; Teplow, D. B. Elucidation of Primary Structure Elements Controlling Early Amyloid β-Protein Oligomerization. J. Biol. Chem., 2003, 278, 34882-34889.
103. Kirkitadze, M. D.; Condron, M. M.; Teplow, D. B. Identification and Characterization of Key Kinetic Intermediates in Amyloid β-Protein Fibrillogenesis. J Mol Biol, 2001, 312, 1103-1119.
104. Streltsov, V.; Varghese, J.; Masters, C.; Nuttall, S. Crystal Structure of the Amyloid-β p3 Fragment Provides a Model for Oligomer Formation in Alzheimer's Disease. J. Neurosci., 2011, 31, 1419-1426.
105. Lockhart, C.; Kim, S.; Kumar, R.; Klimov, D. K. Does amino acid sequence determine the properties of Aβ dimmer? J. Chem. Phys., 2011, 135, 035103.
106. Strodel, B.; Lee, J.; Whittleston, C.; Wales, D. Transmembrane Structures for Alzheimer's Aβ1-42 Oligomers. J. Am. Chem. Soc., 2010, 132, 13300-13312.
107. Lin, H.; Bhatia, R.; Lal, R. Amyloid beta protein forms ion channels: implications for Alzheimer's disease pathophysiology. FASEB J., 2001, 15, 2433-2444.
108. Quist, A.; Doudevski, I.; Lin, H.; Azimova, R.; Ng, D.; Frangione, B.; Kagan, B.; Ghiso, J.; Lal, R. Amyloid ion channels: A common structural link for protein-misfolding disease. Proc. Natl. Acad. Sci. USA., 2005, 102, 10427-10432.
109. Tycko, R.; Sciarretta, K.; Orgel, J.; Meredith, S. Evidence for novel β-sheet structures in Iowa mutant β-amyloid fibrils. Biochemistry, 2009, 48, 6072-6084.
110. van Groen, T.; Wiesehan, K.; Funke, S. A.; Kadish, I.; Nagel-Steger, L.; Willbold, D. In vitro and in vivo Staining Characteristics of Small, Fluorescent, Aβ42-Binding D-Enantiomeric Peptides in Transgenic AD Mouse Models. Chem Med Chem, 2008, 3, 1848-1852.
111. Funke, S. A.; van Groen, T.; Kadish, I.; Bartnik, D.; Nagel-Steger, O., L. Brener; Sehl, T.; Batra-Safferling, R.; Moriscot, C.; Schoehn, G.; Horn, A. H. C.; Muller-Schiffmann, A.; Korth, C.; Sticht, H.; Willbold, D. Oral Treatment with the D-Enantiomeric Peptide D3 Improves the Pathology and Behavior of Alzheimer's Disease Transgenic Mice. ACS Chem. Neurosci., 2010, 1, 639-648.
112. Wiesehan, K.; Buder, K.; Linke, R. P.; Patt, S.; Stoldt, M.; Unger, E.; Schmitt, B.; Bucci, E.; Willbold, D. Selection of D-Amino-Acid peptides that bind to Alzheimer's disease amyloid peptide Aβ(1-42) by mirror image phage display. Chem Bio Chem, 2003, 4, 748-753.
113. Fradinger, E.; Monien, B. H.; Urbanc, B.; Lomakin, A.; Tan, M.; Li, H.; Spring, S. M.; Condron, M. M.; Cruz, L.; Xie, C.-W.; Benedek, G. B.; Bitan, G. C-terminal peptides coassemble into Aβ42 oligomers and protect neurons against Aβ42-induced neurotoxicity. Proc. Natl. Acad. Sci. USA., 2008, 105, 14175-14180.
114. Li, H.; Monien, B. H.; Fradinger, E. A.; Urbanc, B.; Bitan, G. Biophysicsl Characterization of Aβ42 C-terminal Fragments: Inhibitors of Aβ42 Neurotoxicity. Biochemistry, 2010, 49, 1259-1267.
115. Li, H.; Monien, B. H.; Lomakin, A.; Zemel, R.; Fradinger, E. A.; Tan, M.; Spring, S. M.; Urbanc, B.; Xie, C.-W.; Benedek, G. B.; Bitan, G. Mechanistic Investigation of the Inhibition of Aβ42 Assembly and Neurotoxicity by C-terminal Aβ42 Fragments. Biochemistry, 2010, 49, 6358-6364.
116. Wu, C.; Murray, M. M.; Bernstein, S. L.; Condron, M. M.; Bitan, G.; Shea, J.; Bowers, M. T. The Structure of Aβ42 C-Terminal Fragments Probed by a Combined Experimental and Theoretical Study. J. Mol. Biol., 2009, 387, 492-501.
117. Urbanc, B.; Betnel, M.; Cruz, L.; Li, H.; Fradinger, E.; Monien, B. H.; Bitan, G. Structural Basis of Aβ1-42 Toxicity Inhibition by Aβ C-Terminal Fragments: Discrete Molecular Dynamics Study. J. Mol. Biol., 2011, 410, 316-328.
118. Gessel, M. M.; Wu, C.; Li, H.; Bitan, G.; Shea, J.-E.; Bowers, M. T. Aβ(39-42) modulates Aβ42 oligomerization but not fibril formation. Biochemistry, 2011, 51, 108-117.
119. Miller, Y.; Ma, B.; Nussinov, R. Polymorphism in Alzheimer Aβ Amyloid Organization Reflects Conformational Selection in a Rugged Energy Landscape. Chem. Rev., 2010, 110, 4820-4838.
120. Serem, W. K.; Bett, C. K.; Ngunjiri, J. N.; Garno, J. C. Studies of the Growth, Evolution, and Self-Aggregation of β-Amyloid Fibrils Using Tapping-Mode Atomic Force Microscopy. Micros. Res. Tech., 2011, 74, 699-708.
121. Sachse, C.; Faendrich, M.; Grigorieff, N. Paired β-sheet structure of an Aβ(1-40) amyloid fibril revealed by electron microscopy. Proc. Natl. Acad. Sci. USA., 2008, 105, 7462-7466.
122. Petkova, A. T.; Yau, W.-M.; Tycko, R. Experimental Constraints on Quaternary Structure in Alzheimer's β-Amyloid Fibrils. Biochemistry, 2006, 45, 498-512.
123. Luhrs, T.; Ritter, C.; Adrian, M.; Riek-Loher, D.; Bohrmann, B.; Dobeli, H.; Schubert, D.; Riek, R. 3D structure of Alzheimer's amyloid-β (1-42) fibrils. Proc. Natl. Acad. Sci. USA., 2005, 102, 17342-17347.
124. Ma, B.; Nussinov, R. Stabilities and conformations of Alzheimer's β-amyloid peptide oligomers (Aβ16-22, Aβ16-35, and Aβ10-35): sequence effects. Proc. Natl. Acad. Sci. USA., 2002, 99, 14126-14131.
125. Kirschner, D. A.; Abraham, C.; Selkoe, D. J. X-ray diffraction from intraneuronal paired helical filaments and extraneuronal amyloid fibers in Alzheimer disease indicates cross- conformation. Proc. Natl. Acad. Sci. USA., 1986, 83, 503-507.
126. Petkova, A. T.; Ishii, Y.; Balbach, J. J.; Antzutkin, O. N.; Leapman, R. D.; Delaglio, F.; Tycko, R. A structural model for Alzheimer's β-amyloid fibrils based on experimental constraints from solid state NMR. Proc. Natl. Acad. Sci. USA., 2002, 99, 16742-16747.
127. Petkova, A. T.; Leapman, R. D.; Guo, Z.; Yau, W.-M.; Mattson, M. P.; Tycko, R. Self- Propagating, Molecular-Level Polymorphism in Alzheimer's β-Amyloid Fibrils. Science, 2005, 307, 262-265.
128. Buchete, N.-V.; Tycko, R.; Hummer, G. Molecular Dynamics Simulations of Alzheimer's β-Amyloid Protofilaments. J. Mol. Biol., 2005, 353, 804-821.
129. Wu, C.; Bowers, M. T.; Shea, J.-E. Molecular Structures of Quiescently- Grown and Brain- Derived Polymorphic Fibrils of the Alzheimer Amyloid Aβ9-40 Peptide: A Comparison to Agitated Fibrils. PLoS Comp. Biol., 2010, 6, e1000693.
130. Zheng, J.; Jang, H.; Ma, B.; Tsai, C.-J.; Nussinov, R. Molecular dynamics simulations of Alzheimer Aβ (40) elongation and lateral association. Front Biosci., 2008, 13, 3919-3930.
131. Zheng, J.; Jang, H.; Ma, B.; Tsai, C.-J.; Nussinov, R. Modeling the Alzheimer Aβ(17-42) fibril architecture: Tight intermolecular sheet-sheet association and intramolecular hydrated cavities. Biophys. J., 2007, 93, 3046-3057.
132. Buchete, N.-V.; Hummer, G. Structure and dynamics of parallel β-sheets, hydrophobic core, and loops in Alzheimer's Aβ fibrils. Biophys. J., 2007, 92, 3032-3039.
133. Lemkul, J. A.; Bevan, D. R. Assessing the Stability of Alzheimer's Amyloid Protofibrils Using Molecular Dynamics. J. Phys. Chem. B, 2010, 114, 1652-1660.
134. Xu, Z.; Paparcone, R.; Buehler, M. J. Alzheimer's Aβ(1-40) Amyloid Fibrils Feature Size- Dependent Mechanical Properties. Biophys. J., 2010, 98, 2053-2062.
135. Paparcone, R.; Pires, M. A.; Buehler, M. J. Mutations Alter the Geometry and Mechanical Properties of Alzheimer's Aβ(1-40) Amyloid Fibrils. Biochemistry, 2010, 49, 8967-8977.
136. Paravastu, A. K.; Qahwash, I.; Leapman, R. D.; Meredith, S. C.; Tycko, R. Seeded growth of β-amyloid fibrils from Alzheimer's brain-derived fibrils produces a distinct fibril structure. Proc. Natl. Acad. Sci. USA., 2009, 106, 7443-7448.
137. Miller, Y.; Ma, B.; Nussinov, R. The Unique Alzheimer's β- Amyloid Triangular Fibril Has a Cavity along the Fibril Axis under Physiological Conditions. J. Am. Chem. Soc., 2011, 133, 2742-2748.
138. Zheng, J.; Yu, X.; Wang, J.; Yang, J.-C.; Wang, Q. Molecular Modeling of Two Distinct Triangular Oligomers in Amyloid β-Protein. J. Phys. Chem. B, 2010, 114, 463-470.
139. Lam, A. R.; Jiang, J.; Mukamel, S. Distinguishing Amyloid Fibril Structures in Alzheimer's Disease (AD) by Two-Dimensional Ultraviolet (2DUV) Spectroscopy. Biochemistry, 2011, 50, 9809-9816.
140. Zhang, R.; Hu, X.; Khant, H.; Ludtke, S. J.; Chiu, W.; Schmid, M. F.; Frieden, C.; Lee, J.-M. Interprotofilament interactions between Alzheimer's Aβ (1-42) peptides in amyloid fibrils revealed by cryoEM. Proc. Natl. Acad. Sci. USA., 2009, 106, 4653-4658.
141. Miller, Y.; Ma, B.; Tsai, C.-J.; Nussinov, R. Hollow core of Alzheimer's Aβ(42) amyloid observed by cryoEM is relevant at physiological pH. Chem. Rev., 2010, 107, 14128-14133.
142. Zheng, J.; Jang, H.; Ma, B.; Nussinov, R. Annular structures as intermediates in fibril formation of Alzheimer Aβ(17-42). J. Phys. Chem. B, 2008, 112, 6856-6865.
143. Connelly, L.; Jang, H.; Arce, F. T.; Ramachandran, S.; Kagan, B. L.; Nussinov, R.; Lal, R. Effects of Point Substitutions on the Structure of Toxic Alzheimer's β-Amyloid Channels: Atomic Force Microscopy and Molecular Dynamics Simulations. Biochemistry, 2012, 51, 3031-3038.
144. Jang, H.; Arce, F. T.; Ramachandran, S.; Capone, R.; Lal, R.; Nussinov, R. β-Barrel Topology of Alzheimer's β-Amyloid Ion Channels. J. Mol. Biol., 2010, 404, 917-934.
145. Wu, C.; Bowers, M. T.; Shea, J. E. On the Origin of the Stronger Binding of PIB over Thioflavin T to Protofibrils of the Alzheimer Amyloid-β Peptide: A Molecular Dynamics Study. Biophys. J., 2011, 100, 1316-1324.
146. Lemkul, J. A.; Bevan, D. R. Destabilizing Alzheimer's Aβ42 Protofibrils with Morin: Mechanistic Insights from Molecular Dynamics Simulations. Biochemistry, 2010, 49, 3935-3946.
147. Raman, E. P.; Takeda, T.; Klimov, D. K. Molecular Dynamics Simulations of Ibuprofen Binding to Aβ Peptides. Biophys. J., 2009, 97, 2070-2079.
148. Chang, W.; Takeda, T.; Raman, E.; Klimov, D. Molecular Dynamics Simulations of Anti- Aggregation Effect of Ibuprofen. Biophys. J., 2010, 98, 2662-2670.
149. Takeda, T.; Kumar, R.; Raman, E. P.; Klimov, D. K. Nonsteroidal Anti-Inflammatory Drug Naproxen Destabilizes Aβ Amyloid Fibrils: A Molecular Dynamics Investigation. J. Phys. Chem. B, 2010, 114, 15394-15402.
150. Barrow, C. J.; Yasuda, A.; Kenny, P. T.; Zagorski, M. G. Solution Conformations and Aggregational Properties of Synthetic Amyloid b -Peptides of Alzheimer's Disease. Analysis of Circular Dichroism Spectra. J. Mol. Biol., 1992, 225, 1075-1093.
151. Hou, L.; Shao, H.; Zhang, Y.; Li, H.; Menon, N. K.; Neuhaus, E. B.; Brewer, J. M.; Byeon, I.-J. L.; Ray, D. G.; Vitek, M. P.; Iwashita, T.; Makula, R. A.; Przybyla, A. B.; Zagorski, M. G. 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., 2004, 126, 1992-2005.
152. Wood, G. P. F.; Rothlisberger, U. Secondary Structure Assignment of Amyloid-b Peptide Using Chemical Shifts. J. Chem. Theo. Comput., 2011, 7, 1552-1563.
153. Vitalis, A.; Caflisch, A. Micelle-Like Architecture of the Monomer Ensemble of Alzheimer's Amyloid-β Peptide in Aqueous Solution and Its Implications for Aβ Aggregation. J. Mol. Biol., 2010, 403, 148-165.
154. Sawaya, M. R.; Sambashivan, S.; Nelson, R.; Ivanova, M. I.; Sievers, S. A.; Apostol, M. I.; Thompson, M. J.; Balbirnie, M.; Wiltzius, J. J. W.; McFarlane, H. T.; Madsen, A. O.; Riekel, C.; Eisenberg, D. Atomic structures of amyloid cross-β spines reveal varied steric zippers. Nature, 2007, 447, 453-457.
155. Kayed, R.; Head, E.; Thompson, J. L.; McIntire, T. M.; Milton, S. C.; Cotman, C. W.; Glabe, C. G. Common structure of soluble amyloid oligomers implies common mechanisms of pathogenesis. Science., 2003, 300, 486-489.
156. Dahlgren, K. N.; Manelli, A. M.; Stine, W. B.; Baker, L. K.; Krafft, G. A.; LaDu, M. J. Oligomeric and Fibrillar Species of Amyloid-β Peptides Differentially Affect Neuronal Viability. J. Biol. Chem., 2002, 277, 32046-32053.
157. Maiti, P.; Lomakin, A.; Benedek, G.; Bitan, G. Despite its role in assembly, methionine 35 is not necessary for amyloid β-protein toxicity. J. Neurochem., 2010, 113, 1252-1262.
158. Williams, T.; Day, I.; Serpell, L. The Effect of Alzheimer's Aβ Aggregation State on the Permeation of Biomimetic Lipid Vesicles. Langmuir, 2010, 26, 17260-17268.
159. Williams, T.; Johnson, B.; Urbanc, B.; Jenkins, T.; Connell, S.; Serpell, L. Alzheimer's Aβ42 oligomers but not fibrils simultaneously bind to and cause damage to ganglioside containing lipid membranes. Biochem. J., 2011, 439, 67-77.
160. Luheshi, L. M.; Tartaglia, G. G.; Brorsson, A. C.; Pawar, A. P.; Watson, I. E.; Chiti, F.; Vendruscolo, M.; Lomas, D. A.; Dobson, C. M.; Crowther, D. Systematic In vivo Analysis of the Intrinsic Determinants of Amyloid Pathogenicity. PLoS Biol., 2007, 5, e290.
161. Jin, M.; Shepardson, N.; Yang, T.; Chen, G.; Walsh, D.; Selkoe, D. J. Soluble amyloid β-protein dimers isolated from Alzheimer cortex directly induce Tau hyperphosphorylation and neuritic degeneration. Proc. Natl. Acad. Sci. USA., 2011, 108, 5819-5824.
162. Fede, G. D. et al. A Recessive Mutation in the APP Gene with Dominant-Negative Effect on Amyloidogenesis. Science, 2009, 323, 1473-1477.
163. Jonsson, T. et al. A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. Nature, 2012, [Epub ahead of print].
164. Williams, T.; Serpell, L. Membrane and surface interactions of Alzheimer's Aβ peptide - insights into the mechanism of cytotoxicity. FEBS J., 2011, 278, 3905-3917.
165. Kawarabayashi, T.; Shoji, M.; Younkin, L. H.; Wen-Lang, L.; Dickson, D. W.; Murakami, T.; Matsubara, E.; Abe, K.; Ashe, K. H.; Younkin, S. G. Dimeric Amyloid Protein Rapidly Accumulates in Lipid Rafts followed by Apolipoprotein E and Phosphorylated Tau Accumulation in the Tg2576 Mouse Model of Alzheimer's disease. J. Neurosci., 2004, 24, 3801-3809.
166. Ashe, K. H. A Tale about Tau. N. Engl. J. Med., 2007, 357, 933-935.