Inhibiting effect of αₛ₁-casein on Aβ₁–₄₀ fibrillogenesis

BACKGROUND: αₛ₁-Casein is one of the four types of caseins, the largest protein component of bovine milk. The lack of a compact folded conformation and the capability to form micelles suggest a relationship of αₛ₁-casein with the class of the intrinsically disordered (or natively unfolded) proteins. These proteins are known to exert a stabilizing activity on biomolecules through specific interaction with hydrophobic surfaces. In the present work we focused on the effect of αₛ₁-casein on the fibrillogenesis of 1–40 β-amyloid peptide, involved in Alzheimer's disease. METHODS: The aggregation kinetics of β-peptide in presence and absence of αₛ₁-casein was followed under shear at 37°C by recording the Thioflavine fluorescence, usually taken as an indicator of fibers formation. Measurements of Static and Dynamic Light Scattering, Circular Dichroism, and AFM imaging were done to reveal the details of αₛ₁-casein–Aβ₁–₄₀ interaction. RESULTS AND DISCUSSIONS: αₛ₁-Casein addition sizably increases the lag-time of the nucleation phase and slows down the entire fibrillization process. αₛ₁-Casein sequesters the amyloid peptide on its surface thus exerting a chaperone-like activity by means a colloidal inhibition mechanism. GENERAL SIGNIFICANCE: Insights on the working mechanism of natural chaperones in preventing or controlling the amyloid aggregation.