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

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  • Hossein Mohammad-Beigi
  • Atiyeh Hosseini, Center of Excellence in Complex Systems and Condensed Matter (CSCM) , Sharif University of Technology , Tehran 1458889694 , Iran.
  • ,
  • Mohsen Adeli, Department of Biology, Chemistry, Pharmacy, Institute of Chemistry and Biochemistry , Freie University Berlin , 14195 Berlin , Germany.
  • ,
  • Mohammad Reza Ejtehadi, Department of Physics , Sharif University of Technology , P.O. Box 11155-9161, Tehran 1245 , Iran.
  • ,
  • Gunna Christiansen
  • Cagla Sahin
  • ,
  • Zhaoxu Tu, Department of Biology, Chemistry, Pharmacy, Institute of Chemistry and Biochemistry , Freie University Berlin , 14195 Berlin , Germany.
  • ,
  • Mahdi Tavakol, Department of Mechanical Engineering , Sharif University of Technology , Tehran 1245 , Iran.
  • ,
  • Arezou Dilmaghani-Marand, Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute , Tehran University of Medical Sciences , Tehran 1411713137 , Iran.
  • ,
  • Iraj Nabipour, Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute , Bushehr University of Medical Sciences , Bushehr 75147 , Iran.
  • ,
  • Farshad Farzadfar, Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute , Tehran University of Medical Sciences , Tehran 1411713137 , Iran.
  • ,
  • Daniel Erik Otzen
  • Morteza Mahmoudi, Department of Anesthesiology, Brigham and Women's Hospital , Harvard Medical School , Boston , Massachusetts 02115 , United States.
  • ,
  • Mohammad Javad Hajipour, Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute , Bushehr University of Medical Sciences , Bushehr 75147 , Iran.

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.

OriginalsprogEngelsk
TidsskriftACS Nano
Vol/bind13
Nummer3
Sider (fra-til)3243-3256
Antal sider14
ISSN1936-0851
DOI
StatusUdgivet - 2019

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