The potential inhibitory effect of β-casein on the aggregation and deposition of A1-42 fibrils in Alzheimer's disease: insight from in-vitro and in-silico studies

A(1-40) and A(1-42) have been shown to be the main components of the amyloid plaques found in the extracellular environment of neurons in Alzheimer's disease. -Casein, a milk protein, has been shown to display a remarkable chaperone ability in preventing the aggregation of proteins. In this study, the ability of -casein to suppress the amyloid fibril formation of A(1-42) has been examined through in vitro studies and molecular docking simulation. The results demonstrate the inhibitory effect of -casein on fibril formation in A(1-42), in a concentration dependent manner, suggesting that the chaperone binds to the A(1-42) and prevents amyloid fibril formation. Molecular docking results show that the inhibitory effect of the -casein may be due to binding of the chaperone with the aggregation-prone region of the A(1-42) mainly via hydrophobic interactions. -Casein probably binds to the CHC and C-terminal domain of the A(1-42,) and stabilizes proteins by inhibiting the conversion of monomeric A(1-42) into fibrils. Thus our data suggests that the hydrophobic interactions between -casein and A(1-42) play an important role in the burial of the hydrophobic part of the A(1-42.) This means that -casein maybe considered for use in preventing amyloid fibril formation in degenerative diseases such as Alzheimer.