Folic acid inhibits the amyloid fibrils formation of β-lactoglobulin

It is well known that amyloid fibrils are associated with a lot of neurodegenerative diseases. Thus, inhibition of protein aggregation and disruption of the formed amyloid fibrils have been attractive therapeutic strategies for amyloid-associated diseases. Here, we take the widely studied protein, β-lactoglobulin (β-LG), as a model protein to study the inhibition of amyloid fibrils. Using multiple biophysical and biochemical approaches, we successfully identify that folic acid can strongly inhibit amyloid fibrils formation of β-LG in 5 M urea solution. In the presence of folic acid, both the nucleation step and elongation step of β-LG fibrillation can be affected and the suppression efficiency followed a dose depended manner. Furthermore, the studies of protein intrinsic-fluorescence and anilinonaphthalene-8-sulfonic acid (ANS) fluorescence demonstrated that the folic acid decreased the hydrophobicity of the urea-denatured β-LG and changed the conformation of β-LG. Our study provides a convenient way to inhibit the amyloid fibrils formation, which has potential help to study the mechanism of amyloid-diseases.