Influence of curcumin on the Al(iii)-induced conformation transition of silk fibroin and resulting potential therapy for neurodegenerative diseases

Abstract

Neurodegenerative diseases involve the disorder of protein folding in which normally soluble proteins are deposited as abnormally insoluble fibrils that disrupt tissue structure and cause disease. Aluminum ion, Al(III), is known to induce formation of the insoluble β-sheet-rich fibrils, while curcumin is considered capable of binding both metal ions and neurodegenerative disease-related proteins. In the present work, silk fibroin (SF) which have essential and sufficient amino acid sequences for the protein fibrillation on nucleation-dependent conformation transition mechanism similar to that for the fibrillation of neurodegenerative proteins, was used as a model protein to reveal the influence of curcumin on Al(III)-induced conformation transition of proteins. It was demonstrated that Al(III) could induce the conformation of SF into β-sheet, while curcumin could inhibit the event. In particular, Al(III)–curcumin complexes formed at [Al(III)]/[curcumin] ratios from 1 : 1 to 1 : 2 could reverse the conformation of SF from β-sheet into random coil. These findings would be of revelatory significance for developing an efficient approach inhibiting the fibrillation of neurodegenerative proteins.