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