journal article·2019-03-26

Mechanistic Understanding of the Interactions between Nano-Objects with Different Surface Properties and α-Synuclein

Hossein Mohammad-Beigi, Atiyeh Hosseini, Mohsen Adeli, Mohammad Reza Ejtehadi, Gunna Christiansen, Cagla Sahin, Zhaoxu Tu, Mahdi Tavakol, Arezou Dilmaghani-Marand, Iraj Nabipour, Farshad Farzadfar, Daniel Erik Otzen, Morteza Mahmoudi, Mohammad Javad Hajipour

ACS Nano· Volume 13· Issue 3
Publisher page

Abstract

Aggregation of the natively unfolded protein α-synuclein (α-syn) is key to the development of Parkinson's disease (PD). Some nanoparticles (NPs) can inhibit this process and in turn be used for treatment of PD. Using simulation strategies, we show here that α-syn self-assembly is electrostatically driven. Dimerization by head-to-head monomer contact is triggered by dipole-dipole interactions and subsequently stabilized by van der Waals interactions and hydrogen bonds. Therefore, we hypothesized that charged nano-objects could interfere with this process and thus prevent α-syn fibrillation. In our simulations, positively and negatively charged graphene sheets or superparamagnetic iron oxide NPs first interacted with α-syn's N/C terminally charged residues and then with hydrophobic residues in the non-amyloid-β component (61-95) region. In the experimental setup, we demonstrated that the charged nano-objects have the capacity not only to strongly inhibit α-syn fibrillation (both nucleation and elongation) but also to disaggregate the mature fibrils. Through the α-syn fibrillation process, the charged nano-objects induced the formation of off-pathway oligomers.
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Research context

OpenAlex topics: Conducting polymers and applications · Electrochemical sensors and biosensors · Attention Deficit Hyperactivity Disorder

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, DK−8000 Aarhus C, Denmark

Institute for Nanoscience and Nanotechnology (INST), Sharif University of Technology, Tehran 1458889694, Iran

Center of Excellence in Complex Systems and Condensed Matter (CSCM), Sharif University of Technology, Tehran 1458889694, Iran

Faculty of Science, Lorestan University, Khorramabad, Iran

Department of Biology, Chemistry, Pharmacy, Institute of Chemistry and Biochemistry, Freie University Berlin, 14195 Berlin, Germany

School of Nano Science, Institute for Research in Fundamental Sciences (IPM), P.O. Box 19395-5531, Tehran, Iran

Department of Physics, Sharif University of Technology, P.O. Box 11155-9161, Tehran 1245, Iran

Department of Biomedicine-Medical Microbiology and Immunology, Aarhus University, 8000 Aarhus C, Denmark

Science for Life Laboratory, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solnavägen 9, 171 65 Stockholm, Sweden

Department of Mechanical Engineering, Sharif University of Technology, Tehran 1245, Iran

Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran 1411713137, Iran

Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr 75147, Iran

Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 14, DK−8000 Aarhus C, Denmark

Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States

Funding

Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences

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