Influence of Cortisol on the Fibril Formation Kinetics of A?42 Peptide: A Multi-Technical Approach

Amyloid-? peptide (A?) aggregates are known to be correlated with pathological neurode-generative diseases. The fibril formation process of such peptides in solution is influenced by several factors, such as the ionic strength of the buffer, concentration, pH, and presence of other molecules, just to mention a few. In this paper, we report a detailed analysis of in vitro A?42 fibril formation in the presence of cortisol at different relative concentrations. The thioflavin T fluorescence assay allowed us to monitor the fibril formation kinetics, while a morphological characterization of the aggregates was obtained by atomic force microscopy. Moreover, infrared absorption spectroscopy was exploited to investigate the secondary structure changes along the fibril formation path. Molecular dynamics calculations allowed us to understand the intermolecular interactions with cortisol. The combined results demonstrated the influence of cortisol on the fibril formation process: indeed, at cortisol-A?42 concentration ratio (?) close to 0.1 a faster organization of A?42 fragments into fibrils is promoted, while for ? = 1 the formation of fibrils is completely inhibited.