scholarly journals Polyphenols Modulate Alzheimer’s Amyloid Beta Aggregation in a Structure-Dependent Manner

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 756 ◽  
Author(s):  
Huong Phan ◽  
Kaouthar Samarat ◽  
Yuzuru Takamura ◽  
Auriane Azo-Oussou ◽  
Yasutaka Nakazono ◽  
...  
Keyword(s):  
Amyloid Beta ◽  
Self Assembly ◽  
Structural Features ◽  
Hydroxyl Groups ◽  
Dependent Manner ◽  
Force Microscopy ◽  
Atomic Force ◽  
Aggregation Property ◽  
Aβ Aggregation ◽  
Aβ Fibrils

Some polyphenols, which are common natural compounds in fruits, vegetables, seeds, and oils, have been considered as potent inhibitors of amyloid beta (Aβ) aggregation, one critical pathogenic event in Alzheimer’s disease (AD). However, the mechanisms by which polyphenols affect aggregation are not fully understood. In this study, we aimed to investigate the effect of two classes of polyphenols (flavonoids and stilbenes) on the self-assembly of Aβ_42, in particular, how this relates to structure. We found that the flavonoids gallocatechin gallate (GCG) and theaflavin (TF) could completely inhibit Aβ aggregation, while two stilbenes, resveratrol and its glucoside derivative piceid, could also suppress Aβ aggregation, but to a much lesser extent. Intriguingly, resveratrol accelerated the formation of Aβ fibrils before its decreasing effect on fibrillation was detected. Atomic force microscopy (AFM) images showed a huge mass of long and thin Aβ fibrils formed in the presence of resveratrol. Although the morphology was the same in the presence of piceid, the fibrils were sparse in the presence of picead. In the presence of flavonoids, Aβ morphology was unchanged from prior to incubation (0 h), in agreement with amyloid beta kinetics analysis using thioflavin-T fluorescence assay. The electrochemical data showed a higher ability of GCG and TF to interact with Aβ than resveratrol and piceid, which could be attributed to the presence of more aromatic rings and hydroxyl groups. In addition, the two flavonoids exhibited a similar propensity for Aβ aggregation, despite having some differences in their structure. However, in the case of stilbenes, the addition of a glucoside at C-7 slightly decreased anti-Aβ aggregation property compared to resveratrol. These findings contribute to a better understanding of the essential structural features of polyphenols required for inhibiting Aβ aggregation, and the possible mechanisms for modulating aggregation.

scholarly journals The Clustering of mApoE Anti-Amyloidogenic Peptide on Nanoparticle Surface Does Not Alter Its Performance in Controlling Beta-Amyloid Aggregation

2020 ◽  
Vol 21 (3) ◽  
pp. 1066
Author(s):  
Roberta Corti ◽  
Alysia Cox ◽  
Valeria Cassina ◽  
Luca Nardo ◽  
Domenico Salerno ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Force Microscopy ◽  
Atomic Force ◽  
Nanoparticle Surface ◽  
Afm Imaging ◽  
Aggregation Processes ◽  
Aβ Aggregation ◽  
Aβ Fibrils ◽  
Binding Sequence ◽  
The Brain

The deposition of amyloid-β (Aβ) plaques in the brain is a significant pathological signature of Alzheimer’s disease, correlating with synaptic dysfunction and neurodegeneration. Several compounds, peptides, or drugs have been designed to redirect or stop Aβ aggregation. Among them, the trideca-peptide CWG-LRKLRKRLLR (mApoE), which is derived from the receptor binding sequence of apolipoprotein E, is effectively able to inhibit Aβ aggregation and to promote fibril disaggregation. Taking advantage of Atomic Force Microscopy (AFM) imaging and fluorescence techniques, we investigate if the clustering of mApoE on gold nanoparticles (AuNP) surface may affect its performance in controlling Aβ aggregation/disaggregation processes. The results showed that the ability of free mApoE to destroy preformed Aβ fibrils or to hinder the Aβ aggregation process is preserved after its clustering on AuNP. This allows the possibility to design multifunctional drug delivery systems with clustering of anti-amyloidogenic molecules on any NP surface without affecting their performance in controlling Aβ aggregation processes.

scholarly journals Autoxidation Enhances Anti-Amyloid Potential of Flavone Derivatives

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1428
Author(s):  
Andrius Sakalauskas ◽  
Mantas Ziaunys ◽  
Ruta Snieckute ◽  
Vytautas Smirnovas
Keyword(s):  
Amyloid Beta ◽  
Intensity Change ◽  
Hydroxyl Groups ◽  
Force Microscopy ◽  
Atomic Force ◽  
Tht Fluorescence ◽  
Spectrum Change ◽  
Amyloidogenic Protein ◽  
Before And After ◽  
Initial Molecule

The increasing prevalence of amyloid-related disorders, such as Alzheimer’s or Parkinson’s disease, raises the need for effective anti-amyloid drugs. It has been shown on numerous occasions that flavones, a group of naturally occurring anti-oxidants, can impact the aggregation process of several amyloidogenic proteins and peptides, including amyloid-beta. Due to flavone autoxidation at neutral pH, it is uncertain if the effective inhibitor is the initial molecule or a product of this reaction, as many anti-amyloid assays attempt to mimic physiological conditions. In this work, we examine the aggregation-inhibiting properties of flavones before and after they are oxidized. The oxidation of flavones was monitored by measuring the UV-vis absorbance spectrum change over time. The protein aggregation kinetics were followed by measuring the amyloidophilic dye thioflavin-T (ThT) fluorescence intensity change. Atomic force microscopy was employed to image the aggregates formed with the most prominent inhibitors. We demonstrate that flavones, which undergo autoxidation, have a far greater potency at inhibiting the aggregation of both the disease-related amyloid-beta, as well as a model amyloidogenic protein—insulin. Oxidized 6,2′,3′-trihydroxyflavone was the most potent inhibitor affecting both insulin (7-fold inhibition) and amyloid-beta (2-fold inhibition). We also show that this tendency to autoxidize is related to the positions of the flavone hydroxyl groups.

Specific keratinase derived designer peptides potently inhibit Aβ aggregation resulting in reduced neuronal toxicity and apoptosis

2019 ◽  
Vol 476 (12) ◽  
pp. 1817-1841 ◽  
Author(s):  
Rinky Rajput ◽  
Balasubramani G L ◽  
Ankit Srivastava ◽  
Divya Wahi ◽  
Nidhi Shrivastava ◽  
...  
Keyword(s):  
Self Assembly ◽  
Amyloid Β ◽  
Md Simulations ◽  
New Approach ◽  
Force Microscopy ◽  
Atomic Force ◽  
Aromatic Interactions ◽  
Neuronal Toxicity ◽  
Aβ Aggregation ◽  
Amyloid Diseases

Abstract Compelling evidence implicates self-assembly of amyloid-β (Aβ1–42) peptides into soluble oligomers and fibrils as a major underlying event in Alzheimer's disease (AD) pathogenesis. Herein, we employed amyloid-degrading keratinase (kerA) enzyme as a key Aβ1–42-binding scaffold to identify five keratinase-guided peptides (KgPs) capable of interacting with and altering amyloidogenic conversion of Aβ1–42. The KgPs showed micromolar affinities with Aβ1–42 and abolished its sigmoidal amyloidogenic transition, resulting in abrogation of fibrillogenesis. Comprehensive assessment using dynamic light scattering (DLS), atomic force microscopy (AFM) and Fourier-transform infrared (FTIR) spectroscopy showed that KgPs induced the formation of off-pathway oligomers comparatively larger than the native Aβ1–42 oligomers but with a significantly reduced cross-β signature. These off-pathway oligomers exhibited low immunoreactivity against oligomer-specific (A11) and fibril-specific (OC) antibodies and rescued neuronal cells from Aβ1–42 oligomer toxicity as well as neuronal apoptosis. Structural analysis using molecular docking and molecular dynamics (MD) simulations showed two preferred KgP binding sites (Lys16–Phe20 and Leu28–Val39) on the NMR ensembles of monomeric and fibrillar Aβ1–42, indicating an interruption of crucial hydrophobic and aromatic interactions. Overall, our results demonstrate a new approach for designing potential anti-amyloid molecules that could pave way for developing effective therapeutics against AD and other amyloid diseases.

Rapid, Refined, and Robust Method for Expression, Purification, and Characterization of Recombinant Human Amyloid-beta M1-42

2019 ◽  
Author(s):  
Priya Prakash ◽  
Travis Lantz ◽  
Krupal P. Jethava ◽  
Gaurav Chopra
Keyword(s):  
Amyloid Beta ◽  
Western Blots ◽  
Force Microscopy ◽  
E Coli ◽  
Atomic Force ◽  
Set Up ◽  
Short Time

Amyloid plaques found in the brains of Alzheimer’s disease (AD) patients primarily consists of amyloid beta 1-42 (Ab42). Commercially, Ab42 is synthetized using peptide synthesizers. We describe a robust methodology for expression of recombinant human Ab(M1-42) in Rosetta(DE3)pLysS and BL21(DE3)pLysS competent E. coli with refined and rapid analytical purification techniques. The peptide is isolated and purified from the transformed cells using an optimized set-up for reverse-phase HPLC protocol, using commonly available C18 columns, yielding high amounts of peptide (~15-20 mg per 1 L culture) in a short time. The recombinant Ab(M1-42) forms characteristic aggregates similar to synthetic Ab42 aggregates as verified by western blots and atomic force microscopy to warrant future biological use. Our rapid, refined, and robust technique to purify human Ab(M1-42) can be used to synthesize chemical probes for several downstream in vitro and in vivo assays to facilitate AD research.

Clathrin-Inspired Coating and Stabilization of Liposomes by DNA Self-Assembly

2019 ◽  
Author(s):  
Kevin N. Baumann ◽  
Luca Piantanida ◽  
Javier García-Nafría ◽  
Diana Sobota ◽  
Kislon Voïtchovsky ◽  
...  
Keyword(s):  
Self Assembly ◽  
Mechanical Stability ◽  
Lipid Vesicles ◽  
The Self ◽  
Force Microscopy ◽  
Atomic Force ◽  
Cryo Electron Microscopy ◽  
Further Development ◽  
Liposome Surface ◽  
Dna Coating

The self-assembly of the protein clathrin on biological membranes facilitates essential processes of endocytosis in biological systems and has provided a source of inspiration for materials design by the highly ordered structural appearance. By mimicking the architecture of clathrin self-assemblies to coat liposomes with biomaterials, new classes of hybrid carriers can be derived. Here we present a method for fabricating DNA-coated liposomes by hydrophobically anchoring and subsequently growing a DNA network on the liposome surface which structurally mimics clathrin assemblies. Dynamic light scattering (DLS), ζ-potential and cryo-electron microscopy (cryo-EM) measurements independently demonstrate successful DNA coating. Nanomechanical measurements conducted with atomic force microscopy (AFM) show that the DNA coating enhances the mechanical stability of the liposomes relative to uncoated ones. Furthermore, we provide the possibility to reverse the coating process by triggering the disassembly of the DNA coating through a toehold-mediated displacement reaction. Our results describe a straightforward, versatile, and reversible approach for coating and stabilizing lipid vesicles by an interlaced DNA network. This method has potential for further development towards the ordered arrangement of tailored functionalities on the surfaces of liposomes and for applications as hybrid nanocarrier.

Ball-Milling Graphite Used for Synthesis of Biocompatible Blue Luminescent Graphene Quantum Dots

2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Zhou J ◽  
◽  
Dong Y ◽  
Ma Y ◽  
Zhang T ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Ball Milling ◽  
Graphene Quantum Dots ◽  
Raw Material ◽  
Hydroxyl Groups ◽  
High Quality ◽  
Widespread Application ◽  
Force Microscopy ◽  
Atomic Force ◽  
Transmission Electron

Graphene Quantum Dots (GQDs) have been prepared by oxidationhydrothermal reaction, using ball-milling graphite as the starting materials. The prepared GQDs are endowed with excellent luminescence properties, with the optimum emission of 320nm. Blue photoluminescent emitted from the GQDs under ultraviolet light. The GQDs are ~3nm in width and 0.5~2 nm in thickness, revealed by high-resolution transmission electron microscopy and atomic force microscopy. In addition, Fourier transform infrared spectrum evidences the existence of carbonyl and hydroxyl groups, meaning GQDs can be dispersed in water easily and used in cellar imaging, and blue area inside L929 cells were clearly observed under the fluorescence microscope. Both low price of raw material and simple prepared method contribute to the high quality GQDs widespread application in future.

scholarly journals Morphometric characterization of fibrinogen's αC regions and their role in fibrin self-assembly and molecular organization

Nanoscale ◽  
2017 ◽  
Vol 9 (36) ◽  
pp. 13707-13716 ◽  
Author(s):  
Anna D. Protopopova ◽  
Rustem I. Litvinov ◽  
Dennis K. Galanakis ◽  
Chandrasekaran Nagaswami ◽  
Nikolay A. Barinov ◽  
...  
Keyword(s):  
Atomic Force Microscopy ◽  
Self Assembly ◽  
Molecular Organization ◽  
Microscopy Imaging ◽  
Force Microscopy ◽  
Atomic Force ◽  
Atomic Force Microscopy Imaging ◽  
Morphometric Characterization

High-resolution atomic force microscopy imaging reveals the role of fibrinogen αC regions in the early stages of fibrin self-assembly.

Self-assembly layer-by-layer fabrication using porphyrin dye anion and polycation

2009 ◽  
Vol 13 (07) ◽  
pp. 774-778 ◽  
Author(s):  
Byung-Soon Kim ◽  
Young-A Son
Keyword(s):  
Ultrathin Films ◽  
Self Assembly ◽  
Film Surface ◽  
Layer By Layer ◽  
Preparation Technique ◽  
Force Microscopy ◽  
Atomic Force ◽  
Diallyldimethylammonium Chloride ◽  
Afm Analysis ◽  
Progressive Growth

In this study, self-assembled alternating film using poly(diallyldimethylammonium chloride) (PDDAC) and meso-tetrakis(4-carboxyphenyl)porphyrin (MTCP) was prepared as a multilayer deposition on glass substrate. This preparation technique for dye deposition may provide new feasibilities to achieve the manufacture of ultrathin films for nanotechnology application. The deposition films were characterized by UV-vis spectrophotometer and Atomic Force Microscopy (AFM) analysis. The results of UV-vis spectra showed that the absorbance characteristic of the multilayer films linearly increased with an increased number of PDDAC and MTCP bilayers. AFM analysis showed the film surface was relatively uniform and the progressive growth of layers was determined.

scholarly journals Electric Field Assisted Self-Assembly of Viruses into Colored Thin Films

Nanomaterials ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 1310 ◽  
Author(s):  
James J. Tronolone ◽  
Michael Orrill ◽  
Wonbin Song ◽  
Hyun Soo Kim ◽  
Byung Yang Lee ◽  
...  
Keyword(s):  
Electric Field ◽  
Self Assembly ◽  
Force Microscopy ◽  
Thin Film Coatings ◽  
Atomic Force ◽  
Three Phase ◽  
Constant Rate ◽  
Alignment Technique ◽  
Manufacturing Techniques ◽  
Blue Line

Filamentous viruses called M13 bacteriophages are promising materials for devices with thin film coatings because phages are functionalizable, and they can self-assemble into smectic helicoidal nanofilament structures. However, the existing “pulling” approach to align the nanofilaments is slow and limits potential commercialization of this technology. This study uses an applied electric field to rapidly align the nanostructures in a fixed droplet. The electric field reduces pinning of the three-phase contact line, allowing it to recede at a constant rate. Atomic force microscopy reveals that the resulting aligned structures resemble those produced via the pulling method. The field-assisted alignment results in concentric color bands quantified with image analysis of red, green, and blue line profiles. The alignment technique shown here could reduce self-assembly time from hours to minutes and lend itself to scalable manufacturing techniques such as inkjet printing.

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