Exploring the Transition of Human α-Synuclein from Native to the Fibrillar State: Insights into the Pathogenesis of Parkinson’s Disease

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• 作者：Naveed Ahmad Fazili ; Aabgeena Naeem
• 刊名：Journal of Fluorescence
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：26
• 期：5
• 页码：1659-1669
• 全文大小：2,633 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Biomedicine
  Biophysics and Biomedical Physics
  Biotechnology
  Biochemistry
  Analytical Chemistry
  
• 出版者：Springer Netherlands
• ISSN：1573-4994
• 卷排序：26

文摘

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.