Skip to main content

Advertisement

SpringerLink
Log in

Anti-amyloid Aggregation Activity of Natural Compounds: Implications for Alzheimer’s Drug Discovery

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Several plant-derived natural compounds are known to exhibit anti-amyloid aggregation activity which makes them attractive as potential therapies to treat Alzheimer’s disease. The mechanisms of their anti-amyloid activity are not well known. In this regard, many natural compounds are known to exhibit direct binding to various amyloid species including oligomers and fibrils, which in turn can lead to conformational change in the beta-sheet assembly to form nontoxic aggregates. This review discusses the mechanism of anti-amyloid activity of 16 natural compounds and gives structural details on their direct binding interactions with amyloid aggregates. Our computational investigations show that the physicochemical properties of natural products do fit Lipinski’s criteria and that catechol and catechol-type moieties present in natural compounds act as lysine site-specific inhibitors of amyloid aggregation. Based on these observations, we propose a structural template to design novel small molecules containing site-specific ring scaffolds, planar aromatic and nonaromatic linkers with suitably substituted hydrogen bond acceptors and donors. These studies will have significant implications in the design and development of novel amyloid aggregation inhibitors with superior metabolic stability and blood-brain barrier penetration as potential agents to treat Alzheimer’s disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Wang YJ, Zhou HD, Zhou XF (2006) Clearance of amyloid-beta in Alzheimer's disease: progress, problems and perspectives. Drug Discov Today 11(19-20):931–8

    Article  CAS  PubMed  Google Scholar 

  2. Serrano-Pozo A et al (2011) Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med 1(1):a006189

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297(5580):353–6

    Article  CAS  PubMed  Google Scholar 

  4. Liu YH et al (2012) Immunotherapy for Alzheimer disease: the challenge of adverse effects. Nat Rev Neurol 8(8):465–9

    CAS  PubMed  Google Scholar 

  5. Ehrnhoefer DE et al (2008) EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers. Nat Struct Mol Biol 15(6):558–66

    Article  CAS  PubMed  Google Scholar 

  6. Liu KN et al (2012) Curcumin’s pre-incubation temperature affects its inhibitory potency toward amyloid fibrillation and fibril-induced cytotoxicity of lysozyme. Biochim Biophys Acta 1820(11):1774–86

    Article  CAS  PubMed  Google Scholar 

  7. Ladiwala AR et al (2010) Resveratrol selectively remodels soluble oligomers and fibrils of amyloid Abeta into off-pathway conformers. J Biol Chem 285(31):24228–37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sinha S et al (2012) Comparison of three amyloid assembly inhibitors: the sugar scyllo-inositol, the polyphenol epigallocatechin gallate, and the molecular tweezer CLR01. ACS Chem Neurosci 3(6):451–8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Jonsson T et al (2012) A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline. Nature 488(7409):96–9

    Article  CAS  PubMed  Google Scholar 

  10. Wong PC et al (2002) Genetically engineered mouse models of neurodegenerative diseases. Nat Neurosci 5(7):633–9

    Article  CAS  PubMed  Google Scholar 

  11. Suzuki N et al (1994) An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants. Science 264(5163):1336–40

    Article  CAS  PubMed  Google Scholar 

  12. Kuperstein I et al (2010) Neurotoxicity of Alzheimer’s disease Abeta peptides is induced by small changes in the Abeta42 to Abeta40 ratio. EMBO J 29(19):3408–20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Walsh DM, Selkoe DJ (2004) Oligomers on the brain: the emerging role of soluble protein aggregates in neurodegeneration. Protein Pept Lett 11(3):213–28

    Article  CAS  PubMed  Google Scholar 

  14. Crouch PJ et al (2005) Copper-dependent inhibition of human cytochrome c oxidase by a dimeric conformer of amyloid-beta1-42. J Neurosci 25(3):672–9

    Article  CAS  PubMed  Google Scholar 

  15. Shankar GM et al (2008) Amyloid-beta protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory. Nat Med 14(8):837–42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Pierrot N et al (2004) Intraneuronal amyloid-beta1-42 production triggered by sustained increase of cytosolic calcium concentration induces neuronal death. J Neurochem 88(5):1140–50

    Article  CAS  PubMed  Google Scholar 

  17. Golde TE, Janus C (2005) Homing in on intracellular Abeta? Neuron 45(5):639–42

    Article  CAS  PubMed  Google Scholar 

  18. Levi O et al (2007) Intraneuronal amyloid-beta plays a role in mediating the synergistic pathological effects of apoE4 and environmental stimulation. J Neurochem 103(3):1031–40

    Article  CAS  PubMed  Google Scholar 

  19. Lesne S et al (2006) A specific amyloid-beta protein assembly in the brain impairs memory. Nature 440(7082):352–7

    Article  CAS  PubMed  Google Scholar 

  20. Zou K et al (2002) A novel function of monomeric amyloid beta-protein serving as an antioxidant molecule against metal-induced oxidative damage. J Neurosci 22(12):4833–41

    CAS  PubMed  Google Scholar 

  21. Gilbert BJ (2013) The role of amyloid beta in the pathogenesis of Alzheimer’s disease. J Clin Pathol 66(5):362–6

    Article  CAS  PubMed  Google Scholar 

  22. Walsh DM, Selkoe DJ (2007) A beta oligomers—a decade of discovery. J Neurochem 101(5):1172–84

    Article  CAS  PubMed  Google Scholar 

  23. Danielsson J et al (2005) The Alzheimer beta-peptide shows temperature-dependent transitions between left-handed 3-helix, beta-strand and random coil secondary structures. FEBS J 272(15):3938–49

    Article  CAS  PubMed  Google Scholar 

  24. Yang DS et al (1999) Manipulating the amyloid-beta aggregation pathway with chemical chaperones. J Biol Chem 274(46):32970–4

    Article  CAS  PubMed  Google Scholar 

  25. Serpell LC et al (2000) Fiber diffraction of synthetic alpha-synuclein filaments shows amyloid-like cross-beta conformation. Proc Natl Acad Sci U S A 97(9):4897–902

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Rochet JC, Lansbury PT Jr (2000) Amyloid fibrillogenesis: themes and variations. Curr Opin Struct Biol 10(1):60–8

    Article  CAS  PubMed  Google Scholar 

  27. Wetzel R (2006) Kinetics and thermodynamics of amyloid fibril assembly. Acc Chem Res 39(9):671–9

    Article  CAS  PubMed  Google Scholar 

  28. Glabe CG (2008) Structural classification of toxic amyloid oligomers. J Biol Chem 283(44):29639–43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ono K, Condron MM, Teplow DB (2009) Structure-neurotoxicity relationships of amyloid beta-protein oligomers. Proc Natl Acad Sci U S A 106(35):14745–50

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Necula M et al (2007) Small molecule inhibitors of aggregation indicate that amyloid beta oligomerization and fibrillization pathways are independent and distinct. J Biol Chem 282(14):10311–24

    Article  CAS  PubMed  Google Scholar 

  31. Butterfield S et al (2012) Chemical strategies for controlling protein folding and elucidating the molecular mechanisms of amyloid formation and toxicity. J Mol Biol 421(2-3):204–36

    Article  CAS  PubMed  Google Scholar 

  32. Wang SS, Chen YT, Chou SW (2005) Inhibition of amyloid fibril formation of beta-amyloid peptides via the amphiphilic surfactants. Biochim Biophys Acta 1741(3):307–13

    Article  CAS  PubMed  Google Scholar 

  33. Yang C et al (2010) Exploration of the mechanism for LPFFD inhibiting the formation of beta-sheet conformation of A beta(1-42) in water. J Mol Model 16(4):813–21

    Article  CAS  PubMed  Google Scholar 

  34. Lazo ND et al (2005) On the nucleation of amyloid beta-protein monomer folding. Protein Sci 14(6):1581–96

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Xu Y et al (2005) Conformational transition of amyloid beta-peptide. Proc Natl Acad Sci U S A 102(15):5403–7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Gazit E (2002) A possible role for pi-stacking in the self-assembly of amyloid fibrils. FASEB J 16(1):77–83

    Article  CAS  PubMed  Google Scholar 

  37. Gazit E (2002) Mechanistic studies of the process of amyloid fibrils formation by the use of peptide fragments and analogues: implications for the design of fibrillization inhibitors. Curr Med Chem 9(19):1725–35

    Article  CAS  PubMed  Google Scholar 

  38. Gazit E (2002) Global analysis of tandem aromatic octapeptide repeats: the significance of the aromatic-glycine motif. Bioinformatics 18(6):880–3

    Article  CAS  PubMed  Google Scholar 

  39. Sarasa M, Pesini P (2009) Natural non-transgenic animal models for research in Alzheimer’s disease. Curr Alzheimer Res 6(2):171–8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Dai X et al (2012) Abeta-40 Y10F increases betafibrils formation but attenuates the neurotoxicity of amyloid-beta peptide. Int J Mol Sci 13(5):5324–37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Barnham KJ et al (2004) Tyrosine gated electron transfer is key to the toxic mechanism of Alzheimer’s disease beta-amyloid. FASEB J 18(12):1427–9

    CAS  PubMed  Google Scholar 

  42. Yang DS et al (2000) Examining the zinc binding site of the amyloid-beta peptide. Eur J Biochem 267(22):6692–8

    Article  CAS  PubMed  Google Scholar 

  43. Schoneich C (2005) Methionine oxidation by reactive oxygen species: reaction mechanisms and relevance to Alzheimer’s disease. Biochim Biophys Acta 1703(2):111–9

    Article  PubMed  CAS  Google Scholar 

  44. Pepeu G, Giovannini MG (2009) Cholinesterase inhibitors and beyond. Curr Alzheimer Res 6(2):86–96

    Article  CAS  PubMed  Google Scholar 

  45. Bush AI (2008) Drug development based on the metals hypothesis of Alzheimer’s disease. J Alzheimers Dis 15(2):223–40

    Article  CAS  PubMed  Google Scholar 

  46. Tougu V et al (2009) Zn(II)- and Cu(II)-induced non-fibrillar aggregates of amyloid-beta (1-42) peptide are transformed to amyloid fibrils, both spontaneously and under the influence of metal chelators. J Neurochem 110(6):1784–95

    Article  CAS  PubMed  Google Scholar 

  47. Sharma AK et al (2013) The effect of Cu and Zn on the Abeta peptide aggregation and cellular toxicity. Metallomics 5(11):1529–36

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Smith DG, Cappai R, Barnham KJ (2007) The redox chemistry of the Alzheimer’s disease amyloid beta peptide. Biochim Biophys Acta 1768(8):1976–90

    Article  CAS  PubMed  Google Scholar 

  49. Tickler AK et al (2005) Methylation of the imidazole side chains of the Alzheimer disease amyloid-beta peptide results in abolition of superoxide dismutase-like structures and inhibition of neurotoxicity. J Biol Chem 280(14):13355–63

    Article  CAS  PubMed  Google Scholar 

  50. Cheng B et al (2013) Inhibiting toxic aggregation of amyloidogenic proteins: a therapeutic strategy for protein misfolding diseases. Biochim Biophys Acta 1830(10):4860–71

    Article  CAS  PubMed  Google Scholar 

  51. Jayasena T et al (2013) The role of polyphenols in the modulation of sirtuins and other pathways involved in Alzheimer’s disease. Ageing Res Rev 12(4):867–883

    Article  CAS  PubMed  Google Scholar 

  52. Ono K et al (2003) Potent anti-amyloidogenic and fibril-destabilizing effects of polyphenols in vitro: implications for the prevention and therapeutics of Alzheimer’s disease. J Neurochem 87(1):172–81

    Article  CAS  PubMed  Google Scholar 

  53. Rezai-Zadeh K et al (2005) Green tea epigallocatechin-3-gallate (EGCG) modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice. J Neurosci 25(38):8807–14

    Article  CAS  PubMed  Google Scholar 

  54. Lopez del Amo JM et al (2012) Structural properties of EGCG-induced, nontoxic Alzheimer’s disease Abeta oligomers. J Mol Biol 421(4-5):517–24

    Article  CAS  PubMed  Google Scholar 

  55. Bieschke J et al (2010) EGCG remodels mature alpha-synuclein and amyloid-beta fibrils and reduces cellular toxicity. Proc Natl Acad Sci U S A 107(17):7710–5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Liu FF et al (2011) Molecular insight into conformational transition of amyloid beta-peptide 42 inhibited by (-)-epigallocatechin-3-gallate probed by molecular simulations. J Phys Chem B 115(41):11879–87

    Article  CAS  PubMed  Google Scholar 

  57. Palhano FL et al (2013) Toward the molecular mechanism(s) by which EGCG treatment remodels mature amyloid fibrils. J Am Chem Soc 135(20):7503–10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Lim GP et al (2001) The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci 21(21):8370–7

    CAS  PubMed  Google Scholar 

  59. Yanagisawa D et al (2011) Curcuminoid binds to amyloid-beta1-42 oligomer and fibril. J Alzheimers Dis 24(Suppl 2):33–42

    CAS  PubMed  Google Scholar 

  60. Hamaguchi T et al (2009) Phenolic compounds prevent Alzheimer’s pathology through different effects on the amyloid-beta aggregation pathway. Am J Pathol 175(6):2557–65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Caesar I et al (2012) Curcumin promotes A-beta fibrillation and reduces neurotoxicity in transgenic Drosophila. PLoS One 7(2):e31424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Zhao LN et al (2012) The effect of curcumin on the stability of Abeta dimers. J Phys Chem B 116(25):7428–35

    Article  CAS  PubMed  Google Scholar 

  63. Baum L, Ng A (2004) Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer’s disease animal models. J Alzheimers Dis 6(4):367–77, 443-9

    Article  CAS  PubMed  Google Scholar 

  64. Sato T et al (2006) Inhibitors of amyloid toxicity based on beta-sheet packing of Abeta40 and Abeta42. Biochemistry 45(17):5503–16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Balasubramanian K (2006) Molecular orbital basis for yellow curry spice curcumin’s prevention of Alzheimer’s disease. J Agric Food Chem 54(10):3512–20

    Article  CAS  PubMed  Google Scholar 

  66. Masuda Y et al (2011) Solid-state NMR analysis of interaction sites of curcumin and 42-residue amyloid beta-protein fibrils. Bioorg Med Chem 19(20):5967–74

    Article  CAS  PubMed  Google Scholar 

  67. Orlando RA et al (2012) A chemical analog of curcumin as an improved inhibitor of amyloid Abeta oligomerization. PLoS One 7(3):e31869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Streltsov VA et al (2008) The structure of the amyloid-beta peptide high-affinity copper II binding site in Alzheimer disease. Biophys J 95(7):3447–56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Lu Y et al (2010) Copper(I) and copper(II) binding to beta-amyloid 16 (Abeta16) studied by electrospray ionization mass spectrometry. Metallomics 2(7):474–9

    Article  CAS  PubMed  Google Scholar 

  70. Zhang X et al (2013) Design and synthesis of curcumin analogues for in vivo fluorescence imaging and inhibiting copper-induced cross-linking of amyloid beta species in Alzheimer’s disease. J Am Chem Soc 135(44):16397–409

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Baur JA, Sinclair DA (2006) Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 5(6):493–506

    Article  CAS  PubMed  Google Scholar 

  72. Huang TC et al (2011) Resveratrol protects rats from Abeta-induced neurotoxicity by the reduction of iNOS expression and lipid peroxidation. PLoS One 6(12):e29102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Jeon SY et al (2007) Beta-secretase (BACE1)-inhibiting stilbenoids from Smilax Rhizoma. Phytomedicine 14(6):403–8

    Article  CAS  PubMed  Google Scholar 

  74. Marambaud P, Zhao H, Davies P (2005) Resveratrol promotes clearance of Alzheimer’s disease amyloid-beta peptides. J Biol Chem 280(45):37377–82

    Article  CAS  PubMed  Google Scholar 

  75. Vingtdeux V et al (2010) AMP-activated protein kinase signaling activation by resveratrol modulates amyloid-beta peptide metabolism. J Biol Chem 285(12):9100–13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Chen J et al (2005) SIRT1 protects against microglia-dependent amyloid-beta toxicity through inhibiting NF-kappaB signaling. J Biol Chem 280(48):40364–74

    Article  CAS  PubMed  Google Scholar 

  77. Ge JF et al (2012) The binding of resveratrol to monomer and fibril amyloid beta. Neurochem Int 61(7):1192–201

    Article  CAS  PubMed  Google Scholar 

  78. Feng Y et al (2009) Resveratrol inhibits beta-amyloid oligomeric cytotoxicity but does not prevent oligomer formation. Neurotoxicology 30(6):986–95

    Article  CAS  PubMed  Google Scholar 

  79. Lu C et al (2013) Design, synthesis, and evaluation of multitarget-directed resveratrol derivatives for the treatment of Alzheimer’s disease. J Med Chem 56(14):5843–5859

    Article  CAS  PubMed  Google Scholar 

  80. Ladiwala AR et al (2011) Polyphenolic glycosides and aglycones utilize opposing pathways to selectively remodel and inactivate toxic oligomers of amyloid beta. Chembiochem 12(11):1749–58

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Ansari MA et al (2009) Protective effect of quercetin in primary neurons against Abeta(1-42): relevance to Alzheimer’s disease. J Nutr Biochem 20(4):269–75

    Article  CAS  PubMed  Google Scholar 

  82. Pocernich CB et al (2011) Nutritional approaches to modulate oxidative stress in Alzheimer’s disease. Curr Alzheimer Res 8(5):452–69

    Article  CAS  PubMed  Google Scholar 

  83. Lu J et al (2010) Quercetin activates AMP-activated protein kinase by reducing PP2C expression protecting old mouse brain against high cholesterol-induced neurotoxicity. J Pathol 222(2):199–212

    Article  CAS  PubMed  Google Scholar 

  84. Shimmyo Y et al (2008) Flavonols and flavones as BACE-1 inhibitors: structure-activity relationship in cell-free, cell-based and in silico studies reveal novel pharmacophore features. Biochim Biophys Acta 1780(5):819–25

    Article  CAS  PubMed  Google Scholar 

  85. Kim H et al (2005) Effects of naturally occurring compounds on fibril formation and oxidative stress of beta-amyloid. J Agric Food Chem 53(22):8537–41

    Article  CAS  PubMed  Google Scholar 

  86. Shimmyo Y et al (2008) Multifunction of myricetin on A beta: neuroprotection via a conformational change of A beta and reduction of A beta via the interference of secretases. J Neurosci Res 86(2):368–77

    Article  CAS  PubMed  Google Scholar 

  87. Akaishi T et al (2008) Structural requirements for the flavonoid fisetin in inhibiting fibril formation of amyloid beta protein. Neurosci Lett 444(3):280–5

    Article  CAS  PubMed  Google Scholar 

  88. Bartolini M et al (2011) Kinetic characterization of amyloid-beta 1-42 aggregation with a multimethodological approach. Anal Biochem 414(2):215–25

    Article  CAS  PubMed  Google Scholar 

  89. Berhanu WM, Masunov AE (2010) Natural polyphenols as inhibitors of amyloid aggregation. Molecular dynamics study of GNNQQNY heptapeptide decamer. Biophys Chem 149(1-2):12–21

    Article  CAS  PubMed  Google Scholar 

  90. Tay WM, da Silva GF, Ming LJ (2013) Metal binding of flavonoids and their distinct inhibition mechanisms toward the oxidation activity of Cu2+-beta-amyloid: not just serving as suicide antioxidants! Inorg Chem 52(2):679–90

    Article  CAS  PubMed  Google Scholar 

  91. DeToma AS et al (2011) Myricetin: a naturally occurring regulator of metal-induced amyloid-beta aggregation and neurotoxicity. ChemBioChem 12(8):1198–201

    Article  CAS  PubMed  Google Scholar 

  92. Fiori J et al (2012) Disclosure of a fundamental clue for the elucidation of the myricetin mechanism of action as amyloid aggregation inhibitor by mass spectrometry. Electrophoresis 33(22):3380–6

    Article  CAS  PubMed  Google Scholar 

  93. Lu JH et al (2011) Baicalein inhibits formation of alpha-synuclein oligomers within living cells and prevents Abeta peptide fibrillation and oligomerisation. ChemBioChem 12(4):615–24

    Article  CAS  PubMed  Google Scholar 

  94. Lemkul JA, Bevan DR (2010) Destabilizing Alzheimer’s Abeta(42) protofibrils with morin: mechanistic insights from molecular dynamics simulations. Biochemistry 49(18):3935–46

    Article  CAS  PubMed  Google Scholar 

  95. Zhao L et al (2013) Apigenin attenuates copper-mediated beta-amyloid neurotoxicity through antioxidation, mitochondrion protection and MAPK signal inactivation in an AD cell model. Brain Res 1492:33–45

    Article  CAS  PubMed  Google Scholar 

  96. Pitozzi V et al (2012) Long-term dietary extra-virgin olive oil rich in polyphenols reverses age-related dysfunctions in motor coordination and contextual memory in mice: role of oxidative stress. Rejuvenation Res 15(6):601–12

    Article  CAS  PubMed  Google Scholar 

  97. Farr SA et al (2012) Extra virgin olive oil improves learning and memory in SAMP8 mice. J Alzheimers Dis 28(1):81–92

    CAS  PubMed  Google Scholar 

  98. Berr C et al (2009) Olive oil and cognition: results from the three-city study. Dement Geriatr Cogn Disord 28(4):357–64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Bazoti FN et al (2006) Noncovalent interaction between amyloid-beta-peptide (1-40) and oleuropein studied by electrospray ionization mass spectrometry. J Am Soc Mass Spectrom 17(4):568–75

    Article  CAS  PubMed  Google Scholar 

  100. Bazoti FN et al (2008) Localization of the noncovalent binding site between amyloid-beta-peptide and oleuropein using electrospray ionization FT-ICR mass spectrometry. J Am Soc Mass Spectrom 19(8):1078–85

    Article  CAS  PubMed  Google Scholar 

  101. Galanakis PA et al (2011) Study of the interaction between the amyloid beta peptide (1-40) and antioxidant compounds by nuclear magnetic resonance spectroscopy. Biopolymers 96(3):316–27

    Article  CAS  PubMed  Google Scholar 

  102. Diomede L et al (2013) Oleuropein aglycone protects transgenic C. elegans strains expressing Abeta42 by reducing plaque load and motor deficit. PLoS One 8(3):e58893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Grossi C et al (2013) The polyphenol oleuropein aglycone protects TgCRND8 mice against ass plaque pathology. PLoS One 8(8):e71702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Chen YP et al (2013) Syntheses and evaluation of novel isoliquiritigenin derivatives as potential dual inhibitors for amyloid-beta aggregation and 5-lipoxygenase. Eur J Med Chem 66:22–31

    Article  CAS  PubMed  Google Scholar 

  105. Tarozzi A et al (2010) Neuroprotective effects of cyanidin 3-O-glucopyranoside on amyloid beta (25-35) oligomer-induced toxicity. Neurosci Lett 473(2):72–6

    Article  CAS  PubMed  Google Scholar 

  106. Ono K et al (2004) Anti-amyloidogenic activity of tannic acid and its activity to destabilize Alzheimer’s beta-amyloid fibrils in vitro. Biochim Biophys Acta 1690(3):193–202

    Article  CAS  PubMed  Google Scholar 

  107. Li G, Pomes R (2013) Binding mechanism of inositol stereoisomers to monomers and aggregates of Abeta(16-22). J Phys Chem B 117(22):6603–13

    Article  CAS  PubMed  Google Scholar 

  108. Mohamed T et al (2013) Tau-derived-hexapeptide 306VQIVYK311 aggregation inhibitors: nitrocatechol moiety as a pharmacophore in drug design. ACS Chem Neurosci 4(12):1559–70

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Landau M et al (2011) Towards a pharmacophore for amyloid. PLoS Biol 9(6):e1001080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Jiang L et al (2013) Structure-based discovery of fiber-binding compounds that reduce the cytotoxicity of amyloid beta. Elife 2:e00857

    PubMed  PubMed Central  Google Scholar 

  111. Eisenberg DS, et al (2013) Pharmacophores for amyloid fibers involved in Alzheimer’s disease. World Patent WO2013010176A2

  112. Miller Y, Ma B, Nussinov R (2010) Polymorphism in Alzheimer Abeta amyloid organization reflects conformational selection in a rugged energy landscape. Chem Rev 110(8):4820–38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Sato M et al (2013) Site-specific inhibitory mechanism for amyloid beta42 aggregation by catechol-type flavonoids targeting the Lys residues. J Biol Chem 288(32):23212–24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Rao PPN et al (2015) Curcumin binding to beta amyloid: a computational study. Chem Biol Drug Des. doi:10.1111/cbdd.12552

    Google Scholar 

  115. Lipinski CA et al (2001) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 46(1-3):3–26

    Article  CAS  PubMed  Google Scholar 

  116. Cirrito JR et al (2003) In vivo assessment of brain interstitial fluid with microdialysis reveals plaque-associated changes in amyloid-beta metabolism and half-life. J Neurosci 23(26):8844–53

    CAS  PubMed  Google Scholar 

  117. Ferri P et al (2015) Enhancement of flavonoid ability to cross the blood-brain barrier of rats by co-administration with alpha-tocopherol. Food Funct 6(2):394–400

    Article  CAS  PubMed  Google Scholar 

  118. Shu XH et al (2015) Diffusion efficiency and bioavailability of resveratrol administered to rat brain by different routes: therapeutic implications. Neurotherapeutics 12(2):491–501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Sinha S et al (2011) Lysine-specific molecular tweezers are broad-spectrum inhibitors of assembly and toxicity of amyloid proteins. J Am Chem Soc 133(42):16958–69

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work is supported by the National Natural Science Foundation of China (grant numbers 81270423 and 81471296) for Y.-J.W. and NSERC-Discovery RGPIN 03830-2014, Mitacs-Canada, and Early Researcher Award from the Ministry of Research and Innovation, Government of Ontario, Canada, for P.P.N.R.

Conflict of interests

The authors declare no financial or other conflicts of interests.

Author information

Authors and Affiliations

  1. Department of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical University, 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, China

    Xian-Le Bu & Yan-Jiang Wang

  2. School of Pharmacy, Health Sciences Campus, University of Waterloo, 200 University Avenue West, Waterloo, Ontario, N2L 3G1, Canada

    Praveen P. N. Rao

Authors
  1. Xian-Le Bu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Praveen P. N. Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yan-Jiang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Praveen P. N. Rao or Yan-Jiang Wang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bu, XL., Rao, P.P.N. & Wang, YJ. Anti-amyloid Aggregation Activity of Natural Compounds: Implications for Alzheimer’s Drug Discovery. Mol Neurobiol 53, 3565–3575 (2016). https://doi.org/10.1007/s12035-015-9301-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-015-9301-4

Keywords

Search

Navigation