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

作者：Fazili Naveed Ahmad; Naeem Aabgeena^*

来源：Biochimie, 2015, 108: 178-185.

DOI：10.1016/j.biochi.2014.11.011

• Atomic force microscopy
• Caffeic acid
• Escitalopram
• Presynaptic protein
• Parkinson's disease
• Transmission electron microscopy

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 alpha-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 a-synuclein fibril formation, helped us in elucidating the passage of an intermediate at 75 mu M concentration of escitalopram. Fibrils of alpha-synuclein were obtained at 100 mu M concentration of escitalopram. Inhibition of alpha-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 mu M. Maximum inhibition was achieved at a concentration of 60 mu M. Fibrillation of alpha-synuclein in presence of escitalopram gives us clue for the negative effects of antidepressant. Inhibitory activity of caffeic acid against alpha-synuclein fibrillation may guide us in designing novel therapeutic drugs for PD.

• 出版日期2015-1