Inhibiting effect of \u3b1s1-casein on A\u3b21\u201340 fibrillogenesis

Background: \u3b1 s1-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 \u3b1 s1-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 \u3b1 s1- casein on the fibrillogenesis of 1-40 \u3b2-amyloid peptide, involved in Alzheimer's disease. Methods: The aggregation kinetics of \u3b2-peptide in presence and absence of \u3b1 s1-casein was followed under shear at 37 \ub0C 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 \u3b1 s1-casein-A\u3b2 1-40 interaction. Results and discussions: \u3b1 s1-Casein addition sizably increases the lag-time of the nucleation phase and slows down the entire fibrillization process. \u3b1 s1-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