Effect of amyloid-beta oligomers on surface hydrophobicity of human transthyretin protein

Transthyretin (TTR)  is a highly conserved 55 kDa homotetrameric protein that exists in several vertebrate species including humans, bacteria, nematodes, and plants. Previous studies have shown a direct interaction between TTR and amyloid beta (Aβ) (the causative agent of Alzheimer's disease), which leads to the inhibition of Aβ aggregation, fibrillar destruction, or both. In recent years, evidence has shown that the oligomeric species of Aβ formed by the aggregation process are more toxic than mature fibrils. Studies have shown that such an oligomeric mediator is modulated by interaction with TTR. However, the exact mechanism of binding of Aβ to TTR has not yet been determined. In this study, after the purification of human transthyretin protein, the inhibitory effects of TTR on the formation of Aβ were shown in different ways, and finally, the role of hydrophobicity interactions in the chaperone activity of TTR was investigated with the help of protein surface hydrophobicity (PSH) measurement studies. The Scatchard diagram for quantitative measurement of PSH indicates an increase in the hydrophobicity of TTR after binding to oligomeric forms of Aβ. The results presented in this research provide insight into the nature and interactions involved in the initial stages of fibril formation in Aβ and its interaction with TTR. The results showed that hydrophobic interactions probably play a role in the binding between TTR and Aβ. Considering the similarity of amyloid formation systems, the described findings of this study can provide a deeper understanding of the pathology of amyloid diseases.