Anti-fibrillation potency of caffeic acid against an antidepressant induced fibrillogenesis of human α-synuclein: Implications for Parkinson's disease

Alpha synuclein is a 14 kDa intrinsically disordered, presynaptic protein whose fibrillation is a critical step in the pathogenesis of Parkinson's disease (PD). A structural investigation of the effect of escitalopram (a selective serotonin reuptake inhibitor) on α-synuclein was performed using ANS and ThT assays, CD, turbidity and Rayleigh scattering measurements as well as atomic force and transmission electron microscopy. Analysing the mechanism of α-synuclein fibril formation, helped us in elucidating the passage of an intermediate at 75 μM concentration of escitalopram. Fibrils of α-synuclein were obtained at 100 μM concentration of escitalopram. Inhibition of α-synuclein fibrillation was brought about by a polyphenolic acid known as caffeic acid which acted in a concentration dependent manner ranging from 10 to 60 μM. Maximum inhibition was achieved at a concentration of 60 μM. Fibrillation of α-synuclein in presence of escitalopram gives us clue for the negative effects of antidepressant. Inhibitory activity of caffeic acid against α-synuclein fibrillation may guide us in designing novel therapeutic drugs for PD. [Display omitted] •Escitalopram is a selective serotonin reuptake inhibitor.•It has served as an environmental factor which triggers the onset of PD.•AFM and TEM depict the formation of fibrils at 100 μM escitalopram.•Caffeic acid has proved to be a potent anti-fibrillating agent.•Caffeic acid has shown inhibitory behavior towards fibrillation.