title: Attenuation of the early events of α-synuclein aggregation: a fluorescence correlation spectroscopy and laser scanning microscopy study in the presence of surface-coated Fe3O4 nanoparticles.
abstract: The aggregation of α-synuclein (A-syn) has been implicated in the pathogenesis of Parkinson's 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.
authors.affiliation: Protein Folding and Dynamics Laboratory Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology , 4, Raja S. C. Mullick Road, Kolkata 700032, India.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Joshi
authors.forename: Sujit
authors.initials: S
authors.lastname: Basak
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Kundu
authors.forename: Goutam
authors.initials: G
authors.lastname: De
authors.forename: Anindita
authors.initials: A
authors.lastname: Mukhopadhyay
authors.forename: Krishnananda
authors.initials: K
authors.lastname: Chattopadhyay
mesh_terms: D019277:Entropy; D052203:Ferrosoferric Oxide / Q000737:chemistry*; D053768:Metal Nanoparticles / Q000737:chemistry*; D018613:Microscopy, Confocal / Q000379:methods*; D046529:Microscopy, Electron, Transmission; D013050:Spectrometry, Fluorescence / Q000379:methods*; D013499:Surface Properties; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D051844:alpha-Synuclein; D052203:Ferrosoferric Oxide