Insulin adsorption onto zinc oxide nanoparticle mediates conformational rearrangement into amyloid-prone structure with enhanced cytotoxic propensity

Asthana, Shreyasi; Hazarika, Zaved; Nayak, Parth Sarathi; Roy, Jyoti; Jha, Anupam Nath; Mallick, Bibekanand; Jha, Suman

doi:10.1016/j.bbagen.2018.10.004

Cited by 27 publications

(14 citation statements)

References 75 publications

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“…Regarding the cytotoxicity effect of NPs alone or in the presence of amyloid fibril, several investigations have also been reported 44,45. Our cellular results suggest that NPs can show substantial impact on protein conformation which may influence the mortality of host/neighbor cells.…”

Section: Discussionsupporting

confidence: 65%

“…Indeed, the effects depend on the physicochemical characteristics of protein and NPs 44. NPs with different physicochemical properties can increase or decrease the fibrillation and corresponding cytotoxicity.…”

Section: Discussionmentioning

confidence: 99%

“…NPs with different physicochemical properties can increase or decrease the fibrillation and corresponding cytotoxicity. For example, Asthana et al, demonstrated that insulin interaction with zinc oxide NPs causes structural rearrangement into amyloid-prone clusters with increased cytotoxic characteristics 44. Also, Rawat et al, reported that cell membranes can act as modulators of amyloid fibrillation and can target cytotoxicity 45.…”

Section: Discussionmentioning

confidence: 99%

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α-synuclein interaction with zero-valent iron nanoparticles accelerates structural rearrangement into amyloid-susceptible structure with increased cytotoxic tendency

Gilan¹,

Rayat²,

Mustafa³

et al. 2019

IJN

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Aim It has been indicated that NPs may change the amyloidogenic steps of proteins and relevant cytotoxicity. Therefore, this report assigned to explore the impact of ZVFe NPs on the amyloidogenicity and cytotoxicity of α-synuclein as one of the many known amyloid proteins. Methods The characterization of α-synuclein at amyloidogenic condition either alone or with ZVFe NPs was carried out by fluorescence, CD, UV-visible spectroscopic methods, TEM study, docking, and molecular modeling. The cytotoxicity assay of α-synuclein amyloid in the absence and presence of ZVFe NPs was also done by MTT, LDH, and flow cytometry analysis. Results ThT fluorescence spectroscopy revealed that ZVFe NPs shorten the lag phase and accelerate the fibrillation rate of α-synuclein. Nile red and intrinsic fluorescence spectroscopy, CD, Congo red adsorption, and TEM studies indicated that ZVFe NP increased the propensity of α-synuclein into the amyloid fibrillation. Molecular docking study revealed that hydrophilic residues, such as Ser-9 and Lys-12 provide proper sites for hydrogen bonding and electrostatic interactions with adsorbed water molecules on ZVFe NPs, respectively. Molecular dynamics study determined that the interacted protein shifted from a natively discorded conformation toward a more packed structure. Cellular assay displayed that the cytotoxicity of α-synuclein amyloid against SH-SY5Y cells in the presence of ZVFe NPs is greater than the results obtained without ZVFe NPs. Conclusion In conclusion, the existence of ZVFe NPs promotes α-synuclein fibrillation at amyloidogenic conditions by forming a potential template for nucleation, the growth of α-synuclein fibrillation and induced cytotoxicity.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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α-synuclein interaction with zero-valent iron nanoparticles accelerates structural rearrangement into amyloid-susceptible structure with increased cytotoxic tendency

Gilan¹,

Rayat²,

Mustafa³

et al. 2019

IJN

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“…For example, Mandal, Debnath, Jana, Jana40 showed that by modifying the surface of Au NPs with trehalose, the amount of protein aggregation decreases, and hence cytotoxicity is greatly reduced. While, it has been shown that the interaction of insulin with zinc oxide NPs results in the structural reconstruction of amyloid clusters and associated cytotoxicity 41. Nevertheless, Samai, Basu, Mati, Bhattacharya42 recently used bare CeO 2 NPs, CeO 2 NPs coated with folic acid (CeO 2 -FA NPs), and CeO 2 NPs coated with polyacrylic acid (CeO 2 -PAA NPs) to prevent the aggregation of lysosomes and amyloid growth.…”

Section: Discussionmentioning

confidence: 99%

Cerium oxide NPs mitigate the amyloid formation of α-synuclein and associated cytotoxicity

Zand¹,

Khaki²,

Salihi³

et al. 2019

IJN

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AimAmong therapeutic proposals for amyloid-associated disorders, special attention has been given to the exploitation of nanoparticles (NPs) as promising agents against aggregation.MethodsIn this paper, the inhibitory effect of cerium oxide (CeO2) NPs against α-synuclein (α-syn) amyloid formation was explored by different methods such as Thioflavin T (ThT) and 8-anilinonaphthalene-1-sulfonic acid (ANS) fluorescence spectroscopy, Congo red adsorption assay, circular dichroism (CD) spectroscopy, transmission electron microscopy (TEM), and bioinformatical approaches. Also, the cytotoxicity of α-syn amyloid either alone or with CeO2 NPs against neuron-like cells (SH-SY5Y) was examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and quantitative real-time polymerase chain reaction (Bax and Bcl-2 gene expression) assays.ResultsThT and ANS fluorescence assays indicated that CeO2 NPs inhibit the formation of aggregated species and hydrophobic patches of α-syn in amyloidogenic conditions, respectively. Congo red and CD assays demonstrated that CeO2 NPs reduce the formation of amyloid species and β-sheets structures of α-syn molecules, respectively. TEM investigation also confirmed that CeO2 NPs limited the formation of well-defined fibrillary structures of α-syn molecules. Molecular docking and dynamic studies revealed that CeO2 NPs could bind with different affinities to α-syn monomer and amyloid species and fibrillar structure of α-syn is disaggregated in the presence of CeO2 NPs. Moreover, cellular assays depicted that CeO2 NPs mitigate the cell mortality, apoptosis, and the ratio of Bax/Bcl-2 gene expression associated with α-syn amyloids.ConclusionIt may be concluded that CeO2 NPs can be used as therapeutic agents to reduce the aggregation of proteins and mitigate the occurrence of neurodegenerative diseases.

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“…They investigated the protein folding mechanism of villin with explicit solvation [42]. Apart from proteins, the technique has been extended to study other relevant biomolecules [43,44] and protein-nanoparticle interactions [45][46][47][48][49]. Simulation of any system revolves around lot of factors.…”

Section: Molecular Dynamics: the Computational Microscopementioning

confidence: 99%

Role of Force Fields in Protein Function Prediction

Hazarika¹,

Rajkhowa²,

Jha³

2021

Homology Molecular Modeling - Perspectives and Applications

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The world today, although, has developed an elaborate health system to fortify against known and unknown diseases, it continues to be challenged by new as well as emerging, and re-emerging infectious disease threats with severity and probable fluctuations. These threats also have varying costs for morbidity and mortality, as well as for a complex set of socioeconomic outcomes. Some of these diseases are often caused by pathogens which use humans as host. In such cases, it becomes paramount responsibility to dig out the source of pathogen survival to stop their population growth. Sequencing genomes has been finessed so much in the 21st century that complete genomes of any pathogen can be sequenced in a matter of days following which; different potential drug targets are needed to be identified. Structure modeling of the selected sequences is an initial step in structure-based drug design (SBDD). Dynamical study of predicted models provides a stable target structure. Results of these in-silico techniques greatly depend on force field (FF) parameters used. Thus, in this chapter, we intend to discuss the role of FF parameters used in protein structure prediction and molecular dynamics simulation to provide a brief overview on this area.

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Insulin adsorption onto zinc oxide nanoparticle mediates conformational rearrangement into amyloid-prone structure with enhanced cytotoxic propensity

Cited by 27 publications

References 75 publications

<p>α-synuclein interaction with zero-valent iron nanoparticles accelerates structural rearrangement into amyloid-susceptible structure with increased cytotoxic tendency</p>

<p>α-synuclein interaction with zero-valent iron nanoparticles accelerates structural rearrangement into amyloid-susceptible structure with increased cytotoxic tendency</p>

<p>Cerium oxide NPs mitigate the amyloid formation of α-synuclein and associated cytotoxicity</p>

Role of Force Fields in Protein Function Prediction

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