Inhibitory Effect of β-Casein on the Amyloid Fibril Formation of Aβ1–40 Associated with Alzheimer’s Disease

Article

Abstract

Alzheimer’s disease is associated with the fibril formation of β-amyloid peptide in extracellular plaque. β-Casein is a milk protein that has shown a remarkable ability to stabilize proteins by inhibiting their protein aggregation and precipitation. The aim of this study was to test in vitro the ability of β-casein to bind the Aβ1–40, change the structure and inhibit the formation of amyloid fibrils in Aβ1–40. Results from the ThT binding assay indicated that incubation of Aβ1–40 with β-casein retarded amyloid fibril formation of Aβ1–40 in a concentration dependent manner such that at a ratio of 1:1 (w:w) led to a significant reduction in the amount of fluorescent intensity. The results from transmission electron microscopy (TEM) also showed that β-casein significantly reduced the number and size of the Aβ1–40 fibrils, suggesting that the chaperone bound to the Aβ1–40 fibrils and/or interacted with the fibrils in some way. ANS results also showed that β-casein significantly decreased the exposed hydrophobic surface in Aβ1–40. Following an ANS binding assay, CD spectroscopy results also showed that incubation of Aβ1–40 resulted in a structural transition to a β-sheet. In the presence of β-casein, however, α-helical conformation was observed which indicated stabilization of the protein. These results reveal the highly efficacious chaperone action of β-casein against amyloid fibril formation of Aβ1–40. These results suggest that in vitro, β-casein binds to the Aβ1–40 fibrils, alters the Aβ1–40 structure and prevents amyloid fibril formation. This approach may result in the identification of a chaperone mechanism for the treatment of neurological diseases.

Keywords

Alzheimer Amyloid fibril Chaperone β-Casein Inhibition 

References

  1. Bellesia G, Shea JE (2009) Effect of beta sheet propensity on peptide aggregation. J Chem Phys 130:145103CrossRefPubMedGoogle Scholar
  2. Berchtold NC, Cotman CW (1998) Evolution in the conceptualization of dementia and Alzheimer’s disease: Greco-Roman period to the 1960s. Neurobiol Aging 19(3):173–189CrossRefPubMedGoogle Scholar
  3. Bhattacharyya J, Santhoshkumar P, Sharma KK (2003) A peptide sequence—YSGVCHTDLHAWHGDWPLPVK[40–60]—in yeast alcohol dehydrogenase prevents the aggregation of denatured substrate proteins. Biochem Biophys Res Commun 307:1–7CrossRefPubMedGoogle Scholar
  4. Bourhim M, Kruzel M, Srikrishnan T, Nicotera T (2007) Linear quantitation of Aβ aggregation using Thioflavin T: reduction in fibril formation by colostrinin. J Neurosci Methods 160:264–268CrossRefPubMedGoogle Scholar
  5. Cardamone M, Puri NK (1993) Spectrofluorimetric assessment of the surface hydrophobicity of proteins. Biochem J 282:589–593CrossRefGoogle Scholar
  6. Carrotta R, Canale C, Diaspro A, Trapani A, San Biagio PL, Bulone D (2012) Inhibiting effect of αs1-casein on Aβ1–40 fibrillogenesis. Biochim Biophys Acta 1820:124–132CrossRefPubMedGoogle Scholar
  7. Cassiano MM, AreÃas JAG (2001) Study of bovine β-casein at water/lipid interface by molecular modeling. J Molec Struct 539:279–288CrossRefGoogle Scholar
  8. Chaney MO, Webster S, Kuo Y, Roher A (1998) Molecular modelling of the AL 42 peptide from Alzheimer’s disease. Protein Eng 11:761–767CrossRefPubMedGoogle Scholar
  9. Danielsson J, Jarvet J, Damberg P, Graslund A (2002) Translational diffusion measured by PFG-NMRon full length and fragments of the Alzheimer Ab(1-40) peptide. Determination of hydrodynamic radii of random coil peptides of varying length. Magn Reson Chem 40:S89–S97CrossRefGoogle Scholar
  10. Dobson CM (1999) Protein misfolding, evolution and disease. Trends Biochem Sci 24:329–332CrossRefPubMedGoogle Scholar
  11. Dobson CM (2001) The structure basis of protein folding and its links with human disease. Phil Trans R Soc Lond B 356:133–145CrossRefGoogle Scholar
  12. Ehrnsperger M, Graber S, Gaestel M, Buchner J (1997) Binding of non-native protein to Hsp25 during heat shock creates a reservoir of folding intermediates for reactivation. EMBO J 16:221–229PubMedCentralCrossRefPubMedGoogle Scholar
  13. Farrell HM Jr, Jimenez-Flores R, Bleck GT, Brown EM, Butler JE, Creamer LK et al (2004) Nomenclature of the proteins of cows’ milk—sixth revision. J Dairy Sci 87(6):1641–1674CrossRefPubMedGoogle Scholar
  14. Forloni G, Tagliavini F, Bugiani F, Salmona M (1996) Amyloid in Alzheimer’s disease and prion-related encephalopathies: studies with synthetic peptides. Prog Neurobiol 49:287–315CrossRefPubMedGoogle Scholar
  15. Gasymov OK, Glasgow BJ (2007) ANS fluorescence: potential to augment the identification of the external binding sites of proteins. Biochim Biophys Acta 1774:403–411PubMedCentralCrossRefPubMedGoogle Scholar
  16. Goldgaber D, Schwarzman A, Bhasin R, Gregori L, Schemechel D, Saunders A et al (1992) Sequestration of Amyloid β-Peptide. Ann N Y Acad Sci 695:139–143CrossRefGoogle Scholar
  17. Guha S, Manna TK, Das KP, Bhattacharyya B (1998) Chaperone-like activity of tubulin. J Biol Chem 273:30077–30080CrossRefPubMedGoogle Scholar
  18. Harper JD, Wong SS, Lieber CM, Lansbury PT Jr (1997) Observation of metastable Aβ amyloid protofibrils by atomic force microscopy. Chem Biol 4:119–125CrossRefPubMedGoogle Scholar
  19. Hartl FU (1996) Molecular chaperones in cellular protein folding. Nature 381:571–580CrossRefPubMedGoogle Scholar
  20. Hartmann T, Bieger SC, Brühl B, Tienari PJ, Ida N, Allsop D et al (1997) Distinct sites of intracellular production for Alzheimer’s disease A beta40/42 amyloid peptides. Nat Med 3(9):1016–1020CrossRefPubMedGoogle Scholar
  21. Husband FA, Wilde PJ, Mackie AR, Garrood MJ (1997) A comparison of the functional and interfacial properties of β-casein and dephosphorylated β-casein. Colloid Interface Sci 195:77–85CrossRefGoogle Scholar
  22. Jarrett JT, Berger EP, LansburyP T Jr (1993) The C-terminus of the beta protein is critical in amyloidogenesis. Ann NY Acad Sci 695(14):4–148Google Scholar
  23. Kayed R, Head E (2003) Common structure of soluble amyloid oligomers implies common mechanism of pathogenesi. Science 300(5618):486–489CrossRefPubMedGoogle Scholar
  24. Kelly JW (2000) Mechanisms of amyloidogenesis. Nat Struct Biol 2000(7):824–826CrossRefGoogle Scholar
  25. Lee GJ, Roseman AM, Saibil HR, Vierling E (1997) A small heat shock protein stably binds heat-denatured model substrates and can maintain a substrate in a folding-competent state. EMBO J 16(3):659–671PubMedCentralCrossRefPubMedGoogle Scholar
  26. Lomakin A, Chung DS, Benedek GB, Kirschner DA (1996) Teplow DB (1996) On the nucleation and growth of amyloid β-protein fibrils: detection of nuclei and quantitation of rate constants. Proc Nat Acad Sci 93:1125–1129PubMedCentralCrossRefPubMedGoogle Scholar
  27. Manna T, Sarkar T, Poddar A, Roychowdhury M, Das KP, Bhattacharyya B (2001) Chaperone-like activity of tubulin. binding and reactivation of unfolded substrate enzymes. J Biol Chem 276(43):39742–39747CrossRefPubMedGoogle Scholar
  28. Matulis D, Baumann CG, Bloomfield VA, Lovrien RE (1998) 1-Anilino-8-Naphtalene Sulfonate as a protein conformational tightening agent. Biopolymers 49:451–458CrossRefGoogle Scholar
  29. Muchowski PJ (2002) Protein misfolding, amyloid formation and neurodegeneration: a critical role for molecular chaperones? Neuron 35:9–12CrossRefPubMedGoogle Scholar
  30. Naiki H, Gejyo F (1999) Kinetic analysis of amyloid fibril formation. Methods Enzymol 309:305–318CrossRefPubMedGoogle Scholar
  31. Nichols MR, Moss MA, Reed DK, Lin WL, Mukhopadhyay R, Hoh JH et al (2002) Growth of β-amyloid(1-40) protofibrils by monomer elongation and lateral association. Characterization of distinct products by light scattering and atomic force microscopy. Biochemistry 41:6115–6127CrossRefPubMedGoogle Scholar
  32. Rekas A, Adda CG, Andrew Aquilina J, Barnham KJ, Sunde M, Galatis D, Williamson NA et al (2004) Interaction of the molecular chaperone aB-crystallin with a-synuclein: effects on amyloid fibril formation and chaperone activity. J Mol Biol 340:1167–1183CrossRefPubMedGoogle Scholar
  33. Schein CH (1990) Solubility as a function of protein structure and solvent components. Nat Biotechnol 8:308–317CrossRefGoogle Scholar
  34. Seilheimer B, Bohrmann B, Bondole L, Muller F, Stuber D, Dobeli H (1997) The toxicity of the Alzheimer’s L-amyoid peptide correlates with a distinct eber morphology. J Struct Biol 119:59–71CrossRefPubMedGoogle Scholar
  35. Serpell LC (2000) Alzheimer’s amyloid fibrils: structure and assembly. Biochim Biophys Acta 1502:16–30CrossRefPubMedGoogle Scholar
  36. Shin RW, Ogino K (1997) Amyloid b-protein Aβ1–40 but not Aβ1–42 contributes to the experimental formation of Alzheimer disease amyloid fibrils in rat brain. J Neurosci 1:8187–8193Google Scholar
  37. Simmons LK, May PC, Tomaselli KJ, Rydel RE, Fuson KS, Brigham EF, Wright S et al (1994) Secondary structure of amyloid beta peptide correlates with neurotoxic activity in vitro. Mol Pharmacol 45(3):373–379PubMedGoogle Scholar
  38. Stege GJJ, Renkawek K, Overkamp PSG, Verschuure P, van Rijk AF, Reijnen-Aalbers A et al (1999) The molecular chaperone αB-crystallin enhances amyloid β neurotoxicity. Biochem Biophys Res Commun 262:152–156CrossRefPubMedGoogle Scholar
  39. Sunde M, Serpell LC, Bartlam M, Fraser PE, Pepys MB, Blake CC (1997) Common core structure of amyloid fibrils by synchrotron X-ray diffraction. J Mol Biol 273(3):729–739CrossRefPubMedGoogle Scholar
  40. Takeda T, Klimov DK (2009) Interpeptide interactions induce helix to strand structural transition in Abeta peptides. Proteins 77(1):1–13PubMedCentralCrossRefPubMedGoogle Scholar
  41. Tycko R (2000) Solid-state NMR as a probe of amyloid fibril structure. Curr Opin Chem Biol 4:500–506CrossRefPubMedGoogle Scholar
  42. van Montfort RL, Basha E, Friedrich KL, Slingsby C, Vierling E (2001) Crystal structure and assembly of a eukaryotic small heat shock protein. Nat Struct Biol 8:1025–1030CrossRefPubMedGoogle Scholar
  43. Wetzel R (2002) Ideas of order for amyloid fibril structure. Structure 8:1031–1036CrossRefGoogle Scholar
  44. Xu S (2007) Aggregation drives “misfolding” in amyloid fiber formation. Amyloid 14:1119–1131CrossRefGoogle Scholar
  45. Zhang X, Fu X, Zhang H, Liu C, Jiao W, Chang Z (2005) Chaperone-like activity of β-casein. Int J Biochem Cell Biol 37:1232–1240CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of Biology, Faculty of ScienceUniversity of Sistan and BaluchestanZahedanIran

Personalised recommendations