Inhibition of Amyloid Fibril Growth and Dissolution of Amyloid Fibrils by Curcumin–Gold Nanoparticles

Palmal, Sharbari; Maity, Amit Ranjan; Singh, Brijesh Kumar; Basu, Sreetama; Jana, Nihar Ranjan; Jana, Nikhil R.

doi:10.1002/chem.201400079

Cited by 147 publications

(142 citation statements)

References 66 publications

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“…In line with these observations, several research groups have studied the effect of small molecule inhibitors on preformed aggregates and oligomers in detail1416171819. Previous studies showed that these molecules bind to pre-fibrillar aggregates, oligomers or fibrils and caused destabilization of aggregates or alters the amyloidogenic pathway27707172. In the current study, when the effect of curcumin and its analogs was tested on the preformed fibrils of α-Syn, it was found that none of these compounds affected the major protein secondary structure (β-sheet) within fibrils, as determined by CD or FTIR (Figs S3 and S4), however, effectively decreased the exposed hydrophobic surface on the fibrils (Fig.…”

Section: Discussionmentioning

confidence: 95%

Effect of curcumin analogs onα-synuclein aggregation and cytotoxicity

Jha

Ghosh

Das

et al. 2016

Sci Rep

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Alpha-synuclein (α-Syn) aggregation into oligomers and fibrils is associated with dopaminergic neuron loss occurring in Parkinson’s disease (PD) pathogenesis. Compounds that modulate α-Syn aggregation and interact with preformed fibrils/oligomers and convert them to less toxic species could have promising applications in the drug development efforts against PD. Curcumin is one of the Asian food ingredient which showed promising role as therapeutic agent against many neurological disorders including PD. However, the instability and low solubility makes it less attractive for the drug development. In this work, we selected various curcumin analogs and studied their toxicity, stability and efficacy to interact with different α-Syn species and modulation of their toxicity. We found a subset of curcumin analogs with higher stability and showed that curcumin and its various analogs interact with preformed fibrils and oligomers and accelerate α-Syn aggregation to produce morphologically different amyloid fibrils in vitro. Furthermore, these curcumin analogs showed differential binding with the preformed α-Syn aggregates. The present data suggest the potential role of curcumin analogs in modulating α-Syn aggregation.

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Section: Discussionmentioning

confidence: 95%

Effect of curcumin analogs onα-synuclein aggregation and cytotoxicity

Jha

Ghosh

Das

et al. 2016

Sci Rep

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“…[6][7][8][9][10][11][12] For instance, amino-modied polystyrene NPs have both acceleration and retardation effects on the Ab brillation process depending on the concentration and coverage of monomers on the particle surfaces. In recent years, the effect of different types of NPs on brillation process, either promoting or inhibiting, has been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

The effect of mesoporous silica nanoparticle surface chemistry and concentration on the α-synuclein fibrillation

et al. 2015

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The aggregation of an amyloid protein, a-synuclein (a-Syn), has been suggested as a potential cause of Parkinson's and several other neurodegenerative diseases. To explore the possibility of using nanoparticle-based therapeutic agents for the treatment of such diseases, we investigated the influence of surface chemistry and concentration of mesoporous silica nanoparticles (MSNPs) on the fibrillation of recombinant human a-Syn protein in the present work. Bare MSNPs as well as MSNPs of different surface functionalities, including 3-(2-aminoethyl amino) propyltrimethoxysilane (AAS), succinic anhydride (carboxyl), and polyethyleneimine (PEI) were prepared and characterized by electron microscopy, zeta potential measurement, Brunauer-Emmett-Teller (BET) isotherms, and FT-IR analyses.The process of a-Syn fibril formation was monitored by Thioflavin T (ThT) assay, atomic force microscopy (AFM) and fluorescence microscopy imaging. The conformation of a-Syn molecules in fibrillar forms and upon adsorption onto MSNPs was investigated by circular dichroism (CD) analysis, and an MTT assay was employed to evaluate the cytotoxicity effects of a-Syn fibrils on a PC12 cell line in the absence and presence of MSNPs. The synthesized MSNPs were spherical and monodisperse with an average size of 83 AE 6 nm. Our results showed that the fibril formation is reduced considerably in the presence of positively-charged MSNPs, i.e. AAS-and PEI-MSNPs, and is enhanced while treated with negatively-charged MSNPs, i.e. bare and carboxyl-MSNPs. Furthermore, it was also demonstrated that increasing the concentration of the MSNPs regardless of their surface chemistry results in greater effects on the fibril formation-promoting or inhibiting for negatively and positively-charged MSNPs respectively. Subsequently, the cytotoxicity of the formed aggregates was noticed to be significantly reduced in the presence of AAS-and PEI-MSNPs in comparison to that in the absence of these MSNPs.These results suggest that the electrostatic charges and concentration of MSNPs play important regulatory roles in the fibrillation process of a-Syn. Thus, the present study contributes towards the better understanding and control of protein fibrillation by nanoparticles which can lead to development of nanoparticle-mediated therapies.

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“…Similar curcumin-loaded PLGA nanoparticles (80-120 nm mean diameter) confirm lack of toxicity, and protect human SK-N-SH neuroblastoma cells from H 2 O 2 -induced elevation of ROS and consumption of glutathione [186]. Curcumin-functionalized, Si-coated, amide/ ester-connected Au nanoparticles (6.11, Figure 6.5, 10-25 nm hydrodynamic diameter) preferentially inhibit the elongation of Ab 40 oligomers, and promote the disaggregation of Ab 40 fibrils [187]. Ab 40 fibrils disaggregated by Au-supported curcumin are less neurotoxic on mouse neural crest-derived neuro2a cells than either native Ab 40 fibrils or soluble curcumin-disassembled Ab 40 fibrils [187].…”

Section: Interfering With (Neuro)toxic Tau Species In the Aggregationmentioning

confidence: 95%

“…Curcumin-functionalized, Si-coated, amide/ ester-connected Au nanoparticles (6.11, Figure 6.5, 10-25 nm hydrodynamic diameter) preferentially inhibit the elongation of Ab 40 oligomers, and promote the disaggregation of Ab 40 fibrils [187]. Ab 40 fibrils disaggregated by Au-supported curcumin are less neurotoxic on mouse neural crest-derived neuro2a cells than either native Ab 40 fibrils or soluble curcumin-disassembled Ab 40 fibrils [187].…”

Section: Interfering With (Neuro)toxic Tau Species In the Aggregationmentioning

confidence: 99%

Targeting Assembly and Disassembly of Protein Aggregates

Seneci

2015

Chemical Modulators of Protein Misfolding and Neurodegenerative Disease

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Inhibition of Amyloid Fibril Growth and Dissolution of Amyloid Fibrils by Curcumin–Gold Nanoparticles

Cited by 147 publications

References 66 publications

Effect of curcumin analogs onα-synuclein aggregation and cytotoxicity

Effect of curcumin analogs onα-synuclein aggregation and cytotoxicity

The effect of mesoporous silica nanoparticle surface chemistry and concentration on the α-synuclein fibrillation

Targeting Assembly and Disassembly of Protein Aggregates

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