TY - JOUR
T1 - Mechanistic Understanding of the Interactions between Nano-Objects with Different Surface Properties and α-Synuclein
AU - Mohammad-Beigi, Hossein
AU - Hosseini, Atiyeh
AU - Adeli, Mohsen
AU - Ejtehadi, Mohammad Reza
AU - Christiansen, Gunna
AU - Sahin, Cagla
AU - Tu, Zhaoxu
AU - Tavakol, Mahdi
AU - Dilmaghani-Marand, Arezou
AU - Nabipour, Iraj
AU - Farzadfar, Farshad
AU - Otzen, Daniel Erik
AU - Mahmoudi, Morteza
AU - Hajipour, Mohammad Javad
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Parkinson's disease
KW - electrostatic interaction
KW - fibrillation
KW - graphene
KW - superparamagnetic iron oxide nanoparticles
KW - α-synuclein
UR - http://www.scopus.com/inward/record.url?scp=85062479145&partnerID=8YFLogxK
U2 - 10.1021/acsnano.8b08983
DO - 10.1021/acsnano.8b08983
M3 - Journal article
C2 - 30810027
SN - 1936-0851
VL - 13
SP - 3243
EP - 3256
JO - ACS Nano
JF - ACS Nano
IS - 3
ER -