Vanilla and its active constituent vanillin as natural inhibitors of tau and α-synuclein fibril formation

Abstract

Neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by pathological deposition of tau and α-synuclein proteins, respectively. In this research, we investigated the therapeutic potential of the volatile compounds of vanilla and its primary constituent vanillin on the fibrillation process of tau and α-synuclein. Volatile molecules were introduced as vapour at a natural rate of diffusion, and their effects were evaluated using experimental techniques such as ThT and ANS fluorescence spectroscopies, circular dichroism spectroscopy, atomic force microscopy, gel electrophoresis and MTT assay. The results of this study indicated the promising inhibitory effects of vanilla and vanillin on the formation of tau and α-synuclein fibrillar structures. The inhibitory effects of vanilla and vanillin were accompanied by the formation of intermediate and oligomeric species (linear and granular) with lower toxicity when compared to tau and α-synuclein fibril samples and preserving the native conformation of the proteins to some extent. Notably, vanilla exhibited higher anti-fibrillary properties on α-synuclein compared to tau protein, suggesting greater potential for therapeutic intervention in PD. The superior effects of vanilla over vanillin may be attributed to the presence of additional volatile compounds in vanilla. These findings highlight the potential of vanilla and vanillin alone as neuroprotective agents in the management of AD and PD.