Inhibitory Effect of [beta]-Casein on the Amyloid Fibril Formation of A[beta]^sub 1-40^ Associated with Alzheimer's Disease

• Published in: International journal of peptide research and therapeutics Vol. 22; no. 1; p. 23
• Main Authors: Ghahghaei, Arezou, Shahraki, Sima
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Nature B.V 01.03.2016
• Subjects: Alzheimer's disease; Inhibitor drugs; Neurodegeneration; Peptides
• ISSN: 1573-3149; 1573-3904
• DOI: 10.1007/s10989-015-9482-8

Alzheimer's disease is associated with the fibril formation of [beta]-amyloid peptide in extracellular plaque. [beta]-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 [beta]-casein to bind the A[beta]^sub 1-40^, change the structure and inhibit the formation of amyloid fibrils in A[beta]^sub 1-40^. Results from the ThT binding assay indicated that incubation of A[beta]^sub 1-40^ with [beta]-casein retarded amyloid fibril formation of A[beta]^sub 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 [beta]-casein significantly reduced the number and size of the A[beta]^sub 1-40^ fibrils, suggesting that the chaperone bound to the A[beta]^sub 1-40^ fibrils and/or interacted with the fibrils in some way. ANS results also showed that [beta]-casein significantly decreased the exposed hydrophobic surface in A[beta]^sub 1-40^. Following an ANS binding assay, CD spectroscopy results also showed that incubation of A[beta]^sub 1-40^ resulted in a structural transition to a [beta]-sheet. In the presence of [beta]-casein, however, [alpha]-helical conformation was observed which indicated stabilization of the protein. These results reveal the highly efficacious chaperone action of [beta]-casein against amyloid fibril formation of A[beta]^sub 1-40^. These results suggest that in vitro, [beta]-casein binds to the A[beta]^sub 1-40^ fibrils, alters the A[beta]^sub 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.