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

• Published in: International journal of peptide research and therapeutics Vol. 22; no. 1; pp. 23 - 29
• Main Authors: Ghahghaei, Arezou, Shahraki, Sima
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.03.2016
• Subjects: Animal Anatomy; Biochemistry; Biomedical and Life Sciences; Histology; Life Sciences; Molecular Medicine; Morphology; Pharmaceutical Sciences/Technology; Pharmacology/Toxicology; Polymer Sciences; β-Casein; Inhibition; Amyloid fibril; Alzheimer; Chaperone
• ISSN: 1573-3149; 1573-3904
• DOI: 10.1007/s10989-015-9482-8

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 Aβ 1–40 , change the structure and inhibit the formation of amyloid fibrils in Aβ 1–40 . Results from the ThT binding assay indicated that incubation of Aβ 1–40 with β-casein retarded amyloid fibril formation of Aβ 1–40 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 Aβ 1–40 fibrils, suggesting that the chaperone bound to the Aβ 1–40 fibrils and/or interacted with the fibrils in some way. ANS results also showed that β-casein significantly decreased the exposed hydrophobic surface in Aβ 1–40 . Following an ANS binding assay, CD spectroscopy results also showed that incubation of Aβ 1–40 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 Aβ 1–40 . These results suggest that in vitro, β-casein binds to the Aβ 1–40 fibrils, alters the Aβ 1–40 structure and prevents amyloid fibril formation. This approach may result in the identification of a chaperone mechanism for the treatment of neurological diseases.