Table of Contents Author Guidelines Submit a Manuscript
Journal of Diabetes Research
Volume 2016 (2016), Article ID 2046327, 12 pages
http://dx.doi.org/10.1155/2016/2046327
Review Article

Inhibition of IAPP Aggregation and Toxicity by Natural Products and Derivatives

Biophysics and Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055, USA

Received 28 February 2015; Accepted 15 April 2015

Academic Editor: Ehud Gazit

Copyright © 2016 Amit Pithadia et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. P. A. Rushing, M. M. Hagan, R. J. Seeley, T. A. Lutz, and S. C. Woods, “Amylin: a novel action in the brain to reduce body weight,” Endocrinology, vol. 141, no. 2, pp. 850–853, 2000. View at Google Scholar · View at Scopus
  2. P. Westermark, A. Andersson, and G. T. Westermark, “Islet amyloid polypeptide, islet amyloid, and diabetes mellitus,” Physiological Reviews, vol. 91, no. 3, pp. 795–826, 2011. View at Publisher · View at Google Scholar · View at Scopus
  3. E. L. Opie, “On the relation of chronic interstitial pancreatitis to the islands of Langerhans and to diabetes melutus,” Journal of Experimental Medicine, vol. 5, no. 4, pp. 397–428, 1901. View at Publisher · View at Google Scholar
  4. P. Westermark, C. Wernstedt, E. Wilander, and K. Sletten, “A novel peptide in the calcitonin gene related peptide family as an amyloid fibril protein in the endocrine pancreas,” Biochemical and Biophysical Research Communications, vol. 140, no. 3, pp. 827–831, 1986. View at Publisher · View at Google Scholar · View at Scopus
  5. A. Clark, C. A. Wells, I. D. Buley et al., “Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes,” Diabetes Research, vol. 9, no. 4, pp. 151–159, 1988. View at Google Scholar · View at Scopus
  6. P. Westermark and E. Wilander, “The influence of amyloid deposits on the islet volume in maturity onset diabetes mellitus,” Diabetologia, vol. 15, no. 5, pp. 417–421, 1978. View at Publisher · View at Google Scholar · View at Scopus
  7. D. E. Schlamadinger and A. D. Miranker, “Fiber-dependent and -independent toxicity of islet amyloid polypeptide,” Biophysical Journal, vol. 107, no. 11, pp. 2559–2566, 2014. View at Publisher · View at Google Scholar
  8. H. A. Lashuel, “Membrane permeabilization: a common mechanism in protein-misfolding diseases,” Science of Aging Knowledge Environment, vol. 2005, no. 38, article pe28, 2005. View at Google Scholar · View at Scopus
  9. A. Quist, I. Doudevski, H. Lin et al., “Amyloid ion channels: a common structural link for protein-misfolding disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 30, pp. 10427–10432, 2005. View at Publisher · View at Google Scholar · View at Scopus
  10. T. A. Mirzabekov, M.-C. Lin, and B. L. Kagan, “Pore formation by the cytotoxic islet amyloid peptide amylin,” The Journal of Biological Chemistry, vol. 271, no. 4, pp. 1988–1992, 1996. View at Publisher · View at Google Scholar · View at Scopus
  11. J. D. Green, L. Kreplak, C. Goldsbury et al., “Atomic force microscopy reveals defects within mica supported lipid bilayers induced by the amyloidogenic human amylin peptide,” Journal of Molecular Biology, vol. 342, no. 3, pp. 877–887, 2004. View at Publisher · View at Google Scholar · View at Scopus
  12. M. F. M. Engel, L. Khemtémourian, C. C. Kleijer et al., “Membrane damage by human islet amyloid polypeptide through fibril growth at the membrane,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 16, pp. 6033–6038, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. R. Capone, F. G. Quiroz, P. Prangkio et al., “Amyloid-β-induced ion flux in artificial lipid bilayers and neuronal cells: resolving a controversy,” Neurotoxicity Research, vol. 16, no. 1, pp. 1–13, 2009. View at Publisher · View at Google Scholar · View at Scopus
  14. N. B. Last and A. D. Miranker, “Common mechanism unites membrane poration by amyloid and antimicrobial peptides,” Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 16, pp. 6382–6387, 2013. View at Publisher · View at Google Scholar · View at Scopus
  15. L. Milanesi, T. Sheynis, W.-F. Xue et al., “Direct three-dimensional visualization of membrane disruption by amyloid fibrils,” Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 50, pp. 20455–20460, 2012. View at Publisher · View at Google Scholar · View at Scopus
  16. J. R. Brender, U. H. N. Dürr, D. Heyl, M. B. Budarapu, and A. Ramamoorthy, “Membrane fragmentation by an amyloidogenic fragment of human islet amyloid polypeptide detected by solid-state NMR spectroscopy of membrane nanotubes,” Biochimica et Biophysica Acta, vol. 1768, no. 9, pp. 2026–2029, 2007. View at Publisher · View at Google Scholar · View at Scopus
  17. A. Jan, O. Adolfsson, I. Allaman et al., “Aβ42 neurotoxicity is mediated by ongoing nucleated polymerization process rather than by discrete Aβ42 species,” The Journal of Biological Chemistry, vol. 286, no. 10, pp. 8585–8596, 2011. View at Publisher · View at Google Scholar · View at Scopus
  18. M. F. M. Sciacca, J. R. Brender, D.-K. Lee, and A. Ramamoorthy, “Phosphatidylethanolamine enhances amyloid fiber-dependent membrane fragmentation,” Biochemistry, vol. 51, no. 39, pp. 7676–7684, 2012. View at Publisher · View at Google Scholar · View at Scopus
  19. M. F. M. Sciacca, D. Milardi, G. M. L. Messina et al., “Cations as switches of amyloid-mediated membrane disruption mechanisms: calcium and IAPP,” Biophysical Journal, vol. 104, no. 1, pp. 173–184, 2013. View at Publisher · View at Google Scholar · View at Scopus
  20. J. R. Brender, E. L. Lee, K. Hartman et al., “Biphasic effects of insulin on islet amyloid polypeptide membrane disruption,” Biophysical Journal, vol. 100, no. 3, pp. 685–692, 2011. View at Publisher · View at Google Scholar · View at Scopus
  21. J. R. Brender, J. Krishnamoorthy, M. F. Sciacca et al., “Probing the sources of the apparent irreproducibility of amyloid formation: drastic changes in kinetics and a switch in mechanism due to micellelike oligomer formation at critical concentrations of IAPP,” The Journal of Physical Chemistry B, vol. 119, no. 7, pp. 2886–2896, 2015. View at Publisher · View at Google Scholar
  22. Y. Suzuki, J. R. Brender, K. Hartman, A. Ramamoorthy, and E. N. G. Marsh, “Alternative pathways of human islet amyloid polypeptide aggregation distinguished by 19F nuclear magnetic resonance-detected kinetics of monomer consumption,” Biochemistry, vol. 51, no. 41, pp. 8154–8162, 2012. View at Publisher · View at Google Scholar · View at Scopus
  23. J. A. Williamson and A. D. Miranker, “Direct detection of transient α-helical states in islet amyloid polypeptide,” Protein Science, vol. 16, no. 1, pp. 110–117, 2007. View at Publisher · View at Google Scholar · View at Scopus
  24. I. T. Yonemoto, G. J. A. Kroon, H. J. Dyson, W. E. Balch, and J. W. Kelly, “Amylin proprotein processing generates progressively more amyloidogenic peptides that initially sample the helical state,” Biochemistry, vol. 47, no. 37, pp. 9900–9910, 2008. View at Publisher · View at Google Scholar · View at Scopus
  25. R. Soong, J. R. Brender, P. M. Macdonald, and A. Ramamoorthy, “Association of highly compact type II diabetes related islet amyloid polypeptide intermediate species at physiological temperature revealed by diffusion NMR spectroscopy,” Journal of the American Chemical Society, vol. 131, no. 20, pp. 7079–7085, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. S. M. Vaiana, R. B. Best, W.-M. Yau, W. A. Eaton, and J. Hofrichter, “Evidence for a partially structured state of the amylin monomer,” Biophysical Journal, vol. 97, no. 11, pp. 2948–2957, 2009. View at Publisher · View at Google Scholar · View at Scopus
  27. A. F. Chaffotte, J. Iñaki Guijarro, Y. Guillou, M. Delepierre, and M. E. Goldberg, “The ‘pre-molten globule,’ a new intermediate in protein folding,” Journal of Protein Chemistry, vol. 16, no. 5, pp. 433–439, 1997. View at Publisher · View at Google Scholar · View at Scopus
  28. V. N. Uversky and A. L. Fink, “Conformational constraints for amyloid fibrillation: the importance of being unfolded,” Biochimica et Biophysica Acta—Proteins and Proteomics, vol. 1698, no. 2, pp. 131–153, 2004. View at Publisher · View at Google Scholar · View at Scopus
  29. J. R. Brender, R. P. R. Nanga, N. Popovych, R. Soong, P. M. Macdonald, and A. Ramamoorthy, “The amyloidogenic SEVI precursor, PAP248-286, is highly unfolded in solution despite an underlying helical tendency,” Biochimica et Biophysica Acta—Biomembranes, vol. 1808, no. 4, pp. 1161–1169, 2011. View at Publisher · View at Google Scholar · View at Scopus
  30. S. Vivekanandan, J. R. Brender, S. Y. Lee, and A. Ramamoorthy, “A partially folded structure of amyloid-beta(1-40) in an aqueous environment,” Biochemical and Biophysical Research Communications, vol. 411, no. 2, pp. 312–316, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. K. Yanagi, M. Ashizaki, H. Yagi, K. Sakurai, Y.-H. Lee, and Y. Goto, “Hexafluoroisopropanol induces amyloid fibrils of islet amyloid polypeptide by enhancing both hydrophobic and electrostatic interactions,” The Journal of Biological Chemistry, vol. 286, no. 27, pp. 23959–23966, 2011. View at Publisher · View at Google Scholar · View at Scopus
  32. J. C. Hutton, “The internal pH and membrane potential of the insulin-secretory granule,” Biochemical Journal, vol. 204, no. 1, pp. 171–178, 1982. View at Google Scholar · View at Scopus
  33. Y. Suzuki, J. R. Brender, M. T. Soper et al., “Resolution of oligomeric species during the aggregation of Aβ1−40 using 19F NMR,” Biochemistry, vol. 52, no. 11, pp. 1903–1912, 2013. View at Publisher · View at Google Scholar · View at Scopus
  34. S. B. Padrick and A. D. Miranker, “Islet amyloid: phase partitioning and secondary nucleation are central to the mechanism of fibrillogenesis,” Biochemistry, vol. 41, no. 14, pp. 4694–4703, 2002. View at Publisher · View at Google Scholar · View at Scopus
  35. E. Rhoades and A. Gafni, “Micelle formation by a fragment of human islet amyloid polypeptide,” Biophysical Journal, vol. 84, no. 5, pp. 3480–3487, 2003. View at Publisher · View at Google Scholar · View at Scopus
  36. M. Biancalana and S. Koide, “Molecular mechanism of thioflavin-T binding to amyloid fibrils,” Biochimica et Biophysica Acta—Proteins and Proteomics, vol. 1804, no. 7, pp. 1405–1412, 2010. View at Publisher · View at Google Scholar · View at Scopus
  37. S. A. Hudson, H. Ecroyd, T. W. Kee, and J. A. Carver, “The thioflavin T fluorescence assay for amyloid fibril detection can be biased by the presence of exogenous compounds,” The FEBS Journal, vol. 276, no. 20, pp. 5960–5972, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. F. Meng, P. Marek, K. J. Potter, C. B. Verchere, and D. P. Raleigh, “Rifampicin does not prevent amyloid fibril formation by human islet amyloid polypeptide but does inhibit fibril thioflavin-T interactions: implications for mechanistic studies of β-cell death,” Biochemistry, vol. 47, no. 22, pp. 6016–6024, 2008. View at Publisher · View at Google Scholar · View at Scopus
  39. A. Lockhart, L. Ye, D. B. Judd et al., “Evidence for the presence of three distinct binding sites for the thioflavin T class of Alzheimer's disease PET imaging agents on β-amyloid peptide fibrils,” The Journal of Biological Chemistry, vol. 280, no. 9, pp. 7677–7684, 2005. View at Publisher · View at Google Scholar · View at Scopus
  40. R. W. Hepler, K. M. Grimm, D. D. Nahas et al., “Solution state characterization of amyloid β-derived diffusible ligands,” Biochemistry, vol. 45, no. 51, pp. 15157–15167, 2006. View at Publisher · View at Google Scholar · View at Scopus
  41. A. S. DeToma, J. Krishnamoorthy, Y. Nam et al., “Synthetic flavonoids, aminoisoflavones: interaction and reactivity with metal-free and metal-associated amyloid-beta species,” Chemical Science, vol. 5, no. 12, pp. 4851–4862, 2014. View at Google Scholar
  42. S. Lee, X. Zheng, J. Krishnamoorthy et al., “Rational design of a structural framework with potential use to develop chemical reagents that target and modulate multiple facets of Alzheimer's disease,” Journal of the American Chemical Society, vol. 136, no. 1, pp. 299–310, 2014. View at Publisher · View at Google Scholar · View at Scopus
  43. T. Beghyn, R. Deprez-Poulain, N. Willand, B. Folleas, and B. Deprez, “Natural compounds: leads or ideas? Bioinspired molecules for drug discovery,” Chemical Biology and Drug Design, vol. 72, no. 1, pp. 3–15, 2008. View at Publisher · View at Google Scholar · View at Scopus
  44. B. J. Blanchard, A. Chen, L. M. Rozeboom, K. A. Stafford, P. Weigele, and V. M. Ingram, “Efficient reversal of Alzheimer's disease fibril formation and elimination of neurotoxicity by a small molecule,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 40, pp. 14326–14332, 2004. View at Publisher · View at Google Scholar · View at Scopus
  45. J. H. Jang and Y. J. Surh, “Protective effect of resveratrol on beta-amyloid-induced oxidative PC12 cell death,” Free Radical Biology and Medicine, vol. 34, no. 8, pp. 1100–1110, 2003. View at Publisher · View at Google Scholar · View at Scopus
  46. S. Chakrabarti, M. Sinha, I. G. Thakurta, P. Banerjee, and M. Chattopadhyay, “Oxidative stress and amyloid beta toxicity in Alzheimer's disease: intervention in a complex relationship by antioxidants,” Current Medicinal Chemistry, vol. 20, no. 37, pp. 4648–4664, 2013. View at Publisher · View at Google Scholar · View at Scopus
  47. N. Apetz, G. Munch, S. Govindaraghavan, and E. Gyengesi, “Natural compounds and plant extracts as therapeutics against chronic inflammation in Alzheimer's disease—a translational perspective,” CNS Neurological Disorders—Drug Targets, vol. 13, no. 7, pp. 1175–1191, 2014. View at Publisher · View at Google Scholar
  48. R. Mishra, D. Sellin, D. Radovan, A. Gohlke, and R. Winter, “Inhibiting islet amyloid polypeptide fibril formation by the red wine compound resveratrol,” ChemBioChem, vol. 10, no. 3, pp. 445–449, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. F. Evers, C. Jeworrek, S. Tiemeyer et al., “Elucidating the mechanism of lipid membrane-induced IAPP fibrillogenesis and its inhibition by the red wine compound resveratrol: a synchrotron X-ray reflectivity study,” Journal of the American Chemical Society, vol. 131, no. 27, pp. 9516–9521, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. N. Arispe, J. Diaz, S. R. Durell, Y. Shafrir, and H. R. Guy, “Polyhistidine peptide inhibitor of the Aβ calcium channel potently blocks the Aβ-induced calcium response in cells. Theoretical modeling suggests a cooperative binding process,” Biochemistry, vol. 49, no. 36, pp. 7847–7853, 2010. View at Publisher · View at Google Scholar · View at Scopus
  51. N. Arispe, J. C. Diaz, and O. Simakova, “Aβ ion channels. Prospects for treating Alzheimer's disease with Aβ channel blockers,” Biochimica et Biophysica Acta, vol. 1768, no. 8, pp. 1952–1965, 2007. View at Publisher · View at Google Scholar · View at Scopus
  52. J. C. Diaz, O. Simakova, K. A. Jacobson, N. Arispe, and H. B. Pollard, “Small molecule blockers of the Alzheimer Abeta calcium channel potently protect neurons from Abeta cytotoxicity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 9, pp. 3348–3353, 2009. View at Publisher · View at Google Scholar · View at Scopus
  53. J. Fantini, C. Di Scala, N. Yahi et al., “Bexarotene blocks calcium-permeable ion channels formed by neurotoxic Alzheimer's β-amyloid peptides,” ACS Chemical Neuroscience, vol. 5, no. 3, pp. 216–224, 2014. View at Publisher · View at Google Scholar · View at Scopus
  54. Y. Porat, A. Abramowitz, and E. Gazit, “Inhibition of amyloid fibril formation by polyphenols: structural similarity and aromatic interactions as a common inhibition mechanism,” Chemical Biology and Drug Design, vol. 67, no. 1, pp. 27–37, 2006. View at Publisher · View at Google Scholar · View at Scopus
  55. M. Stefani and S. Rigacci, “Protein folding and aggregation into amyloid: the interference by natural phenolic compounds,” International Journal of Molecular Sciences, vol. 14, no. 6, pp. 12411–12457, 2013. View at Publisher · View at Google Scholar
  56. A. Mähler, S. Mandel, M. Lorenz et al., “Epigallocatechin-3-gallate: a useful, effective and safe clinical approach for targeted prevention and individualised treatment of neurological diseases?” EPMA Journal, vol. 4, no. 1, article 5, 2013. View at Publisher · View at Google Scholar
  57. D. E. Ehrnhoefer, J. Bieschke, A. Boeddrich et al., “EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers,” Nature Structural & Molecular Biology, vol. 15, no. 6, pp. 558–566, 2008. View at Publisher · View at Google Scholar · View at Scopus
  58. F. L. Palhano, J. Lee, N. P. Grimster, and J. W. Kelly, “Toward the molecular mechanism(s) by which EGCG treatment remodels mature amyloid fibrils,” Journal of the American Chemical Society, vol. 135, no. 20, pp. 7503–7510, 2013. View at Publisher · View at Google Scholar · View at Scopus
  59. P. Cao and D. P. Raleigh, “Analysis of the inhibition and remodeling of islet amyloid polypeptide amyloid fibers by flavanols,” Biochemistry, vol. 51, no. 13, pp. 2670–2683, 2012. View at Publisher · View at Google Scholar · View at Scopus
  60. F. Meng, A. Abedini, A. Plesner, C. B. Verchere, and D. P. Raleigh, “The Flavanol (-)-epigallocatechin 3-gallate inhibits amyloid formation by islet amyloid polypeptide, disaggregates amyloid fibrils, and protects cultured cells against IAPP-induced toxicity,” Biochemistry, vol. 49, no. 37, pp. 8127–8133, 2010. View at Publisher · View at Google Scholar · View at Scopus
  61. L. M. Young, J. C. Saunders, R. A. Mahood et al., “Screening and classifying small-molecule inhibitors of amyloid formation using ion mobility spectrometry–mass spectrometry,” Nature Chemistry, vol. 7, no. 1, pp. 73–81, 2014. View at Publisher · View at Google Scholar
  62. N. Popovych, J. R. Brender, R. Soong et al., “Site specific interaction of the polyphenol EGCG with the SEVI amyloid precursor peptide PAP(248–286),” The Journal of Physical Chemistry B, vol. 116, no. 11, pp. 3650–3658, 2012. View at Publisher · View at Google Scholar · View at Scopus
  63. M. F. M. Engel, C. C. Vandenakker, M. Schleeger, K. P. Velikov, G. H. Koenderink, and M. Bonn, “The polyphenol EGCG inhibits amyloid formation less efficiently at phospholipid interfaces than in bulk solution,” Journal of the American Chemical Society, vol. 134, no. 36, pp. 14781–14788, 2012. View at Publisher · View at Google Scholar · View at Scopus
  64. Q. Wang, J. Guo, P. Jiao, H. Liu, and X. Yao, “Exploring the influence of EGCG on the β-sheet-rich oligomers of human islet amyloid polypeptide (hIAPP1-37) and identifying its possible binding sites from molecular dynamics simulation,” PloS ONE, vol. 9, no. 4, Article ID e94796, 2014. View at Google Scholar
  65. S. Sparks, G. Liu, K. J. Robbins, and N. D. Lazo, “Curcumin modulates the self-assembly of the islet amyloid polypeptide by disassembling α-helix,” Biochemical and Biophysical Research Communications, vol. 422, no. 4, pp. 551–555, 2012. View at Publisher · View at Google Scholar · View at Scopus
  66. G. Liu, J. C. Gaines, K. J. Robbins, and N. D. Lazo, “Kinetic profile of amyloid formation in the presence of an aromatic inhibitor by nuclear magnetic resonance,” ACS Medicinal Chemistry Letters, vol. 3, no. 10, pp. 856–859, 2012. View at Publisher · View at Google Scholar · View at Scopus
  67. L.-H. Tu, L. M. Young, A. G. Wong, A. E. Ashcroft, S. E. Radford, and D. P. Raleigh, “Mutational analysis of the ability of resveratrol to inhibit amyloid formation by islet amyloid polypeptide: critical evaluation of the importance of aromatic–inhibitor and histidine–inhibitor interactions,” Biochemistry, vol. 54, no. 3, pp. 666–676, 2015. View at Publisher · View at Google Scholar
  68. F. Lolicato, A. Raudino, D. Milardi, and C. la Rosa, “Resveratrol interferes with the aggregation of membrane-bound human-IAPP: a molecular dynamics study,” European Journal of Medicinal Chemistry, vol. 92, pp. 876–881, 2015. View at Publisher · View at Google Scholar
  69. P. Jiang, W. Li, J.-E. Shea, and Y. Mu, “Resveratrol inhibits the formation of multiple-layered β-sheet oligomers of the human islet amyloid polypeptide segment 22–27,” Biophysical Journal, vol. 100, no. 6, pp. 1550–1558, 2011. View at Publisher · View at Google Scholar · View at Scopus
  70. L. Wei, P. Jiang, W. Xu et al., “The molecular basis of distinct aggregation pathways of islet amyloid polypeptide,” The Journal of Biological Chemistry, vol. 286, no. 8, pp. 6291–6300, 2011. View at Publisher · View at Google Scholar · View at Scopus
  71. D. Radovan, N. Opitz, and R. Winter, “Fluorescence microscopy studies on islet amyloid polypeptide fibrillation at heterogeneous and cellular membrane interfaces and its inhibition by resveratrol,” FEBS Letters, vol. 583, no. 9, pp. 1439–1445, 2009. View at Publisher · View at Google Scholar · View at Scopus
  72. T. Sheynis, A. Friediger, W.-F. Xue et al., “Aggregation modulators interfere with membrane interactions of β2-microglobulin fibrils,” Biophysical Journal, vol. 105, no. 3, pp. 745–755, 2013. View at Publisher · View at Google Scholar · View at Scopus
  73. J. Zhao, R. Hu, M. F. M. Sciacca et al., “Non-selective ion channel activity of polymorphic human islet amyloid polypeptide (amylin) double channels,” Physical Chemistry Chemical Physics, vol. 16, no. 6, pp. 2368–2377, 2014. View at Publisher · View at Google Scholar · View at Scopus
  74. M. F. M. Sciacca, S. A. Kotler, J. R. Brender, J. Chen, D.-K. Lee, and A. Ramamoorthy, “Two-step mechanism of membrane disruption by Aβ through membrane fragmentation and pore formation,” Biophysical Journal, vol. 103, no. 4, pp. 702–710, 2012. View at Publisher · View at Google Scholar · View at Scopus
  75. C. Zelus, A. Fox, A. Calciano, B. S. Faridian, L. A. Nogaj, and D. A. Moffet, “Myricetin inhibits islet amyloid polypeptide (IAPP) aggregation and rescues living mammalian cells from IAPP toxicity,” The Open Biochemistry Journal, vol. 6, pp. 66–70, 2012. View at Publisher · View at Google Scholar · View at Scopus
  76. H. Noor, P. Cao, and D. P. Raleigh, “Morin hydrate inhibits amyloid formation by islet amyloid polypeptide and disaggregates amyloid fibers,” Protein Science, vol. 21, no. 3, pp. 373–382, 2012. View at Publisher · View at Google Scholar · View at Scopus
  77. H. Wang and D. P. Raleigh, “General amyloid inhibitors? A critical examination of the inhibition of IAPP amyloid formation by inositol stereoisomers,” PLoS ONE, vol. 9, no. 9, Article ID e104023, 2014. View at Publisher · View at Google Scholar
  78. B. Cheng, H. Gong, X. Li et al., “Salvianolic acid B inhibits the amyloid formation of human islet amyloid polypeptideand protects pancreatic beta-cells against cytotoxicity,” Proteins: Structure, Function and Bioinformatics, vol. 81, no. 4, pp. 613–621, 2013. View at Publisher · View at Google Scholar · View at Scopus
  79. M. A. Rubio, D. E. Schlamadinger, E. M. White, and A. D. Miranker, “Peptide amyloid surface display,” Biochemistry, vol. 54, no. 4, pp. 987–993, 2015. View at Publisher · View at Google Scholar
  80. A. F. McKoy, J. Chen, T. Schupbach, and M. H. Hecht, “A novel inhibitor of amyloid β (Aβ) peptide aggregation: from high throughput screening to efficacy in an animal model of Alzheimer disease,” The Journal of Biological Chemistry, vol. 287, no. 46, pp. 38992–39000, 2012. View at Publisher · View at Google Scholar · View at Scopus
  81. J. Chen, A. H. Armstrong, A. N. Koehler, and M. H. Hecht, “Small molecule microarrays enable the discovery of compounds that bind the Alzheimer's Aβ peptide and reduce its cytotoxicity,” Journal of the American Chemical Society, vol. 132, no. 47, pp. 17015–17022, 2010. View at Publisher · View at Google Scholar · View at Scopus
  82. W. Kim, Y. Kim, J. Min, D. J. Kim, Y.-T. Chang, and M. H. Hecht, “A high-throughput screen for compounds that inhibit aggregation of the Alzheimer's peptide,” ACS Chemical Biology, vol. 1, no. 7, pp. 461–469, 2006. View at Publisher · View at Google Scholar · View at Scopus
  83. S. Kumar, M. Brown, A. Nath, and A. Miranker, “Folded small molecule manipulation of islet amyloid polypeptide,” Chemistry & Biology, vol. 21, no. 6, pp. 775–781, 2014. View at Publisher · View at Google Scholar
  84. J. A. Hebda, M. Magzoub, and A. D. Miranker, “Small molecule screening in context: lipid-catalyzed amyloid formation,” Protein Science, vol. 23, no. 10, pp. 1341–1348, 2014. View at Publisher · View at Google Scholar
  85. S. Kumar and A. D. Miranker, “A foldamer approach to targeting membrane bound helical states of islet amyloid polypeptide,” Chemical Communications, vol. 49, no. 42, pp. 4749–4751, 2013. View at Publisher · View at Google Scholar · View at Scopus
  86. J. R. Brender, K. Hartman, R. P. R. Nanga et al., “Role of zinc in human islet amyloid polypeptide aggregation,” Journal of the American Chemical Society, vol. 132, no. 26, pp. 8973–8983, 2010. View at Publisher · View at Google Scholar · View at Scopus
  87. A. Masad, L. Hayes, B. J. Tabner et al., “Copper-mediated formation of hydrogen peroxide from the amylin peptide: a novel mechanism for degeneration of islet cells in type-2 diabetes mellitus?” FEBS Letters, vol. 581, no. 18, pp. 3489–3493, 2007. View at Publisher · View at Google Scholar · View at Scopus
  88. E. C. Lee, E. Ha, S. Singh et al., “Copper(II)-human amylin complex protects pancreatic cells from amylin toxicity,” Physical Chemistry Chemical Physics, vol. 15, no. 30, pp. 12558–12571, 2013. View at Publisher · View at Google Scholar · View at Scopus
  89. L. M. Young, P. Cao, D. P. Raleigh, A. E. Ashcroft, and S. E. Radford, “Ion mobility spectrometry-mass spectrometry defines the oligomeric intermediates in amylin amyloid formation and the mode of action of inhibitors,” Journal of the American Chemical Society, vol. 136, no. 2, pp. 660–670, 2014. View at Publisher · View at Google Scholar · View at Scopus
  90. R. Yesuvadian, J. Krishnamoorthy, A. Ramamoorthy, and A. Bhunia, “Potent γ-secretase inhibitors/modulators interact with amyloid-β fibrils but do not inhibit fibrillation: a high-resolution NMR study,” Biochemical and Biophysical Research Communications, vol. 447, no. 4, pp. 590–595, 2014. View at Publisher · View at Google Scholar · View at Scopus
  91. R. Huang, S. Vivekanandan, J. R. Brender, Y. Abe, A. Naito, and A. Ramamoorthy, “NMR characterization of monomeric and oligomeric conformations of human calcitonin and its interaction with EGCG,” Journal of Molecular Biology, vol. 416, no. 1, pp. 108–120, 2012. View at Publisher · View at Google Scholar · View at Scopus
  92. S.-J. Hyung, A. S. DeToma, J. R. Brender et al., “Insights into antiamyloidogenic properties of the green tea extract (−)-epigallocatechin-3-gallate toward metal-associated amyloid-β species,” Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 10, pp. 3743–3748, 2013. View at Publisher · View at Google Scholar · View at Scopus
  93. J. M. L. del Amo, U. Fink, M. Dasari et al., “Structural properties of EGCG-induced, nontoxic Alzheimer's disease Aβ oligomers,” Journal of Molecular Biology, vol. 421, no. 4-5, pp. 517–524, 2012. View at Publisher · View at Google Scholar · View at Scopus
  94. Z. Fu, D. Aucoin, M. Ahmed, M. Ziliox, W. E. Van Nostrand, and S. O. Smith, “Capping of Aβ42 oligomers by small molecule inhibitors,” Biochemistry, vol. 53, no. 50, pp. 7893–7903, 2014. View at Publisher · View at Google Scholar