title: Exploring the Transition of Human α-Synuclein from Native to the Fibrillar State: Insights into the Pathogenesis of Parkinson's Disease.
abstract: The etiology of Parkinson's disease involves the interplay between the environmental and genetic factors. Here in this study human α-synuclein upon exposure to 100 μM pendimethalin for 12 h in vitro passes through a partially folded state which proceeds to the aggregated state and terminally ends in the fibrillar phase. Variations in the ANS fluorescence intensities led to the detection of intermediate and aggregated states at 6 and 10 h respectively. Far-UV CD analysis depicted significant α-helical content for intermediate state at 6 h in presence of 100 μM pendimethalin. Further increasing the incubation time to 12 h resulted in a predominant β-sheet content which was confirmed to be fibrillar by TEM. Turbidity, Rayleigh scattering analysis, Congo red assay and ThT measurements supported the TEM data i.e. the formation of fibrillar structure of human α-synuclein upon 12 h incubation. Thus, our observation could suggest a possible underlying molecular basis for Parkinson's disease. Graphical Abstract Schematic elucidation of the factors involved in the fibrillation of α-Synuclein during Parkinson's pathogenesis.
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. aabgeenanaim@gmail.com.
authors.forename: Aabgeena
authors.initials: A
authors.lastname: Naeem
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology*; D002942:Circular Dichroism; D006540:Herbicides / Q000494:pharmacology; D006801:Humans; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D066329:Protein Aggregates / Q000187:drug effects*; D011487:Protein Conformation / Q000187:drug effects*; D051844:alpha-Synuclein / Q000737:chemistry* / Q000187:drug effects
chemical_list: D000814:Aniline Compounds; D006540:Herbicides; D066329:Protein Aggregates; C497604:SNCA protein, human; D051844:alpha-Synuclein; C030856:pendimethalin
keywords: Congo red; Fibrillar; Parkinson’s; Pendimethalin; Turbidity; α-synuclein