Back to Browse Journals » Research and Reports in Biology » Volume 2

Modulating α-synuclein misfolding and fibrillation in vitro by agrochemicals

Authors Blanca A Silva, Olof Einarsdóttir, Anthony L Fink1, et al

Published Date March 2011 Volume 2011:2 Pages 43—56

DOI http://dx.doi.org/10.2147/RRB.S16448

Published 23 March 2011

Blanca A Silva1, Olof Einarsdóttir1, Anthony L Fink1,†, Vladimir N Uversky2,3
1
Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA, USA; 2Department of Molecular Medicine, University of South Florida, Tampa, FL, USA; 3Institute for Biological Instrumentation, Russian Academy of Sciences, Pushchino, Moscow Region, Russia
Anthony L Fink passed away on March 2, 2008

Abstract: A combination of spectroscopic techniques including atomic force microscopy (AFM) and transmission electron microscopy (TEM), was used to analyze the effect of chemically distinct agrochemicals (pesticides, herbicides, and fungicides) on the in vitro misfolding and aggregation of a presynaptic intrinsically disordered protein α-synuclein. Despite their differences in chemical properties, almost all the compounds screened affected the α-synuclein fibrillation in a concentration-dependent manner. The morphology of the aggregated α-synuclein was characterized by AFM and TEM techniques. In addition to typical fibrils abundantly found at the equilibrium phase, this analysis revealed the existence of a noticeable nonfibrillar fraction where α-synuclein was present as protofilaments, small oligomers, and large oligomeric species. The aggregated α-synuclein samples were separated into soluble and insoluble fractions by ultracentrifugation and subjected to structural and morphological characterization. Attenuated total reflectance Fourier transform infrared spectroscopic analysis showed that the insoluble α-synuclein fractions possessed a high content of ordered β-structure, whereas the β-structure content of the supernatant pool populated by oligomeric species was noticeably lower. This study provides evidence that chemically distinct agrochemicals can directly interact with α-synuclein to induce structural changes and affect the fibrillation process of this important protein.

Keywords: Parkinson's disease, environmental toxins, intrinsically disordered protein

Download Article [PDF] 

Creative Commons License This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution - Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php

Readers of this article also read:

Role of aliskiren in cardio-renal protection and use in hypertensives with multiple risk factors

Eduardo Pimenta, Suzanne Oparil

Vascular Health and Risk Management 2009, 5:453-463

Published Date: 19 May 2009

Thiolated chitosan nanoparticles for enhancing oral absorption of docetaxel: preparation, in vitro and ex vivo evaluation

Shahrooz Saremi, Fatemeh Atyabi, Seyedeh Parinaz Akhlaghi, et al

International Journal of Nanomedicine 2011, 6:119-128

Published Date: 12 January 2011

Duchenne muscular dystrophy gene therapy: Lost in translation?

Dongsheng Duan

Research and Reports in Biology 2011, 2:31-42

Published Date: 4 March 2011

A new beginning

John A Martignetti

Advances in Genomics and Genetics 2011, 1:1-2

Published Date: 16 March 2011

Analysis of radiation-induced genome alterations in Vigna unguiculata

van der Vyver C, Vorster BJ, Kunert KJ, Cullis CA

Research and Reports in Biology 2011, 2:89-99

Published Date: 1 September 2011

The genomics and genetics of ankylosing spondylitis

Kenna TJ, Davidson SI, Thomas GP

Advances in Genomics and Genetics 2011, 1:9-25

Published Date: 16 December 2011

Activities of methionine-γ-lyase in the acidophilic archaeon “Ferroplasma acidarmanus” strain fer1

Khan MA, López-Muñoz MM, Kaspar CW, Hung KF

Research and Reports in Biology 2013, 4:11-22

Published Date: 4 April 2013