title: Anti-fibrillation potency of caffeic acid against an antidepressant induced fibrillogenesis of human α-synuclein: Implications for Parkinson's disease.
abstract: 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.
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202 002, India.
authors.forename: Naveed Ahmad
authors.initials: NA
authors.lastname: Fazili
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202 002, India. Electronic address: aabgeenanaim@gmail.com.
authors.forename: Aabgeena
authors.initials: A
authors.lastname: Naeem
mesh_terms: D000817:Anilino Naphthalenesulfonates / Q000737:chemistry; D000928:Antidepressive Agents / Q000494:pharmacology*; D002109:Caffeic Acids / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D066329:Protein Aggregates / Q000187:drug effects*; D017433:Protein Structure, Secondary / Q000187:drug effects; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: C515594:8-anilino-1-naphthalenesulfonic acid; D000817:Anilino Naphthalenesulfonates; D000928:Antidepressive Agents; D002109:Caffeic Acids; D066329:Protein Aggregates; C497604:SNCA protein, human; D051844:alpha-Synuclein; C040048:caffeic acid
keywords: Atomic force microscopy; Caffeic acid; Escitalopram; Parkinson's disease; Presynaptic protein; Transmission electron microscopy