Attenuation of the Early Events of 伪-Synuclein Aggregation: A Fluorescence Correlation Spectroscopy and Laser Scanning Microscopy Study in the Presence of Surface-Coated Fe3O4 Na

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• 作者：Nidhi Joshi ; Sujit Basak ; Sangeeta Kundu ; Goutam De ; Anindita Mukhopadhyay ; Krishnananda Chattopadhyay
• 刊名：Langmuir
• 出版年：2015
• 出版时间：February 3, 2015
• 年：2015
• 卷：31
• 期：4
• 页码：1469-1478
• 全文大小：595K
• ISSN：1520-5827

文摘

The aggregation of 伪-synuclein (A-syn) has been implicated in the pathogenesis of Parkinson鈥檚 disease (PD). Although the early events of aggregation and not the matured amyloid fibrils are believed to be responsible for the toxicity, it has been difficult to probe the formation of early oligomers experimentally. We studied the effect of Fe₃O₄ nanoparticle (NP) in the early stage of aggregation of A-syn using fluorescence correlation spectroscopy (FCS) and laser scanning microscopy. The binding between the monomeric protein and NPs was also studied using FCS at single-molecule resolution. Our data showed that the addition of bare Fe₃O₄ NPs accelerated the rate of early aggregation, and it did not bind the monomeric A-syn. In contrast, l-lysine (Lys)-coated Fe₃O₄ NPs showed strong binding with the monomeric A-syn, inhibiting the early events of aggregation. Lys-coated Fe₃O₄ NPs showed significantly less cell toxicity compared with bare Fe₃O₄ NPs and can be explored as a possible strategy to develop therapeutic application against PD. To the best of our knowledge, this report is the first example of using a small molecule to attenuate the early (and arguably the most relevant in terms of PD pathogenesis) events of A-syn aggregation.