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

2014 ◽  
Vol 20 (20) ◽  
pp. 6184-6191 ◽  
Author(s):  
Sharbari Palmal ◽  
Amit Ranjan Maity ◽  
Brijesh Kumar Singh ◽  
Sreetama Basu ◽  
Nihar R. Jana ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Amyloid Fibrils ◽  
Amyloid Fibril

scholarly journals The Ultrastructure of Tissue Damage by Amyloid Fibrils

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4611
Author(s):  
Haruki Koike ◽  
Masahisa Katsuno
Keyword(s):  
Tissue Damage ◽  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Prion Diseases ◽  
Nerve Biopsy ◽  
Al Amyloidosis ◽  
Amyloid Fibril Formation ◽  
Autopsy Specimens ◽  
Fibril Aggregates ◽  
Interfering Rna

Amyloidosis is a group of diseases that includes Alzheimer’s disease, prion diseases, transthyretin (ATTR) amyloidosis, and immunoglobulin light chain (AL) amyloidosis. The mechanism of organ dysfunction resulting from amyloidosis has been a topic of debate. This review focuses on the ultrastructure of tissue damage resulting from amyloid deposition and therapeutic insights based on the pathophysiology of amyloidosis. Studies of nerve biopsy or cardiac autopsy specimens from patients with ATTR and AL amyloidoses show atrophy of cells near amyloid fibril aggregates. In addition to the stress or toxicity attributable to amyloid fibrils themselves, the toxicity of non-fibrillar states of amyloidogenic proteins, particularly oligomers, may also participate in the mechanisms of tissue damage. The obscuration of the basement and cytoplasmic membranes of cells near amyloid fibrils attributable to an affinity of components constituting these membranes to those of amyloid fibrils may also play an important role in tissue damage. Possible major therapeutic strategies based on pathophysiology of amyloidosis consist of the following: 1) reducing or preventing the production of causative proteins; 2) preventing the causative proteins from participating in the process of amyloid fibril formation; and/or 3) eliminating already-deposited amyloid fibrils. As the development of novel disease-modifying therapies such as short interfering RNA, antisense oligonucleotide, and monoclonal antibodies is remarkable, early diagnosis and appropriate selection of treatment is becoming more and more important for patients with amyloidosis.

scholarly journals Molecular dynamics simulations of mechanical failure in polymorphic arrangements of amyloid fibrils containing structural defects

2013 ◽  
Vol 4 ◽  
pp. 429-440 ◽  
Author(s):  
Hlengisizwe Ndlovu ◽  
Alison E Ashcroft ◽  
Sheena E Radford ◽  
Sarah A Harris
Keyword(s):  
Mechanical Properties ◽  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Steered Molecular Dynamics ◽  
Mechanical Failure ◽  
Structural Defects ◽  
Dynamics Simulations

We examine how the different steric packing arrangements found in amyloid fibril polymorphs can modulate their mechanical properties using steered molecular dynamics simulations. Our calculations demonstrate that for fibrils containing structural defects, their ability to resist force in a particular direction can be dominated by both the number and molecular details of the defects that are present. The simulations thereby suggest a hierarchy of factors that govern the mechanical resilience of fibrils, and illustrate the general principles that must be considered when quantifying the mechanical properties of amyloid fibres containing defects.

scholarly journals The amphibian antimicrobial peptide uperin 3.5 is a cross-α/cross-β chameleon functional amyloid

2021 ◽  
Vol 118 (3) ◽  
pp. e2014442118
Author(s):  
Nir Salinas ◽  
Einav Tayeb-Fligelman ◽  
Massimo D. Sammito ◽  
Daniel Bloch ◽  
Raz Jelinek ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Membrane Damage ◽  
Fibril Formation ◽  
Regulation Mechanism ◽  
Bacterial Cells ◽  
Amyloid Fibril Formation ◽  
Β Amyloid ◽  
Β Sheets

Antimicrobial activity is being increasingly linked to amyloid fibril formation, suggesting physiological roles for some human amyloids, which have historically been viewed as strictly pathological agents. This work reports on formation of functional cross-α amyloid fibrils of the amphibian antimicrobial peptide uperin 3.5 at atomic resolution, an architecture initially discovered in the bacterial PSMα3 cytotoxin. The fibrils of uperin 3.5 and PSMα3 comprised antiparallel and parallel helical sheets, respectively, recapitulating properties of β-sheets. Uperin 3.5 demonstrated chameleon properties of a secondary structure switch, forming mostly cross-β fibrils in the absence of lipids. Uperin 3.5 helical fibril formation was largely induced by, and formed on, bacterial cells or membrane mimetics, and led to membrane damage and cell death. These findings suggest a regulation mechanism, which includes storage of inactive peptides as well as environmentally induced activation of uperin 3.5, via chameleon cross-α/β amyloid fibrils.

How Changes in the Sequence of the Peptide CLPFFD-NH2Can Modify the Conjugation and Stability of Gold Nanoparticles and Their Affinity for β-Amyloid Fibrils

2008 ◽  
Vol 19 (6) ◽  
pp. 1154-1163 ◽  
Author(s):  
Ivonne Olmedo ◽  
Eyleen Araya ◽  
Fausto Sanz ◽  
Elias Medina ◽  
Jordi Arbiol ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Amyloid Fibrils ◽  
Β Amyloid

scholarly journals Quantification of amyloid fibril polymorphism by nano-morphometry reveals the individuality of filament assembly

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Liam D. Aubrey ◽  
Ben J. F. Blakeman ◽  
Liisa Lutter ◽  
Christopher J. Serpell ◽  
Mick F. Tuite ◽  
...  
Keyword(s):  
Self Assembly ◽  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Biological Function ◽  
Structural Basis ◽  
Distance Curve ◽  
Filament Assembly ◽  
Sample Heterogeneity ◽  
Structural Insights ◽  
Polymorphic Nature

Abstract Amyloid fibrils are highly polymorphic structures formed by many different proteins. They provide biological function but also abnormally accumulate in numerous human diseases. The physicochemical principles of amyloid polymorphism are not understood due to lack of structural insights at the single-fibril level. To identify and classify different fibril polymorphs and to quantify the level of heterogeneity is essential to decipher the precise links between amyloid structures and their functional and disease associated properties such as toxicity, strains, propagation and spreading. Employing gentle, force-distance curve-based AFM, we produce detailed images, from which the 3D reconstruction of individual filaments in heterogeneous amyloid samples is achieved. Distinctive fibril polymorphs are then classified by hierarchical clustering, and sample heterogeneity is objectively quantified. These data demonstrate the polymorphic nature of fibril populations, provide important information regarding the energy landscape of amyloid self-assembly, and offer quantitative insights into the structural basis of polymorphism in amyloid populations.

scholarly journals Metal-dependent inhibition of amyloid fibril formation: synergistic effects of cobalt–tannic acid networks

Nanoscale ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 1921-1928 ◽  
Author(s):  
Wenjie Zhang ◽  
Andrew J. Christofferson ◽  
Quinn A. Besford ◽  
Joseph J. Richardson ◽  
Junling Guo ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Tannic Acid ◽  
Amyloid Fibril ◽  
Synergistic Effects ◽  
Fibril Formation ◽  
Coated Particles ◽  
Amyloid Fibril Formation ◽  
Dependent Inhibition

Cobalt–tannic acid-coated gold nanoparticles are found to better inhibit amyloid fibril formation than other metal-based tannic acid-coated particles.

scholarly journals What Can the Kinetics of Amyloid Fibril Formation Tell about Off-pathway Aggregation?

2015 ◽  
Vol 291 (4) ◽  
pp. 2018-2032 ◽  
Author(s):  
Rosa Crespo ◽  
Eva Villar-Alvarez ◽  
Pablo Taboada ◽  
Fernando A. Rocha ◽  
Ana M. Damas ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Pathogenic Role ◽  
Amyloid Deposits ◽  
Amyloid Fibril Formation ◽  
Microscopy Techniques ◽  
Analytical Tools ◽  
Kinetics Of ◽  
Quantitative Importance

Some of the most prevalent neurodegenerative diseases are characterized by the accumulation of amyloid fibrils in organs and tissues. Although the pathogenic role of these fibrils has not been completely established, increasing evidence suggests off-pathway aggregation as a source of toxic/detoxicating deposits that still remains to be targeted. The present work is a step toward the development of off-pathway modulators using the same amyloid-specific dyes as those conventionally employed to screen amyloid inhibitors. We identified a series of kinetic signatures revealing the quantitative importance of off-pathway aggregation relative to amyloid fibrillization; these include non-linear semilog plots of amyloid progress curves, highly variable end point signals, and half-life coordinates weakly influenced by concentration. Molecules that attenuate/intensify the magnitude of these signals are considered promising off-pathway inhibitors/promoters. An illustrative example shows that amyloid deposits of lysozyme are only the tip of an iceberg hiding a crowd of insoluble aggregates. Thoroughly validated using advanced microscopy techniques and complementary measurements of dynamic light scattering, CD, and soluble protein depletion, the new analytical tools are compatible with the high-throughput methods currently employed in drug discovery.

scholarly journals WALTZ-DB 2.0: an updated database containing structural information of experimentally determined amyloid-forming peptides

2019 ◽  
Vol 48 (D1) ◽  
pp. D389-D393 ◽  
Author(s):  
Nikolaos Louros ◽  
Katerina Konstantoulea ◽  
Matthias De Vleeschouwer ◽  
Meine Ramakers ◽  
Joost Schymkowitz ◽  
...  
Keyword(s):  
Open Access ◽  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Structural Information ◽  
3D Models ◽  
Accurate Prediction ◽  
Binding Assays ◽  
Manual Curation ◽  
Open Access Database ◽  
User Friendly

Abstract Transition of soluble proteins into insoluble amyloid fibrils is driven by self-propagating short sequence stretches. However, accurate prediction of aggregation determinants remains challenging. Here, we describe WALTZ-DB 2.0, an updated and significantly expanded open-access database providing information on experimentally determined amyloid-forming hexapeptide sequences (http://waltzdb.switchlab.org/). We have updated WALTZ-DB 2.0 with new entries, including: (i) experimental validation of an in-house developed dataset of 229 hexapeptides, using electron microscopy and Thioflavin-T binding assays; (ii) manual curation of 98 amyloid-forming peptides isolated from literature. Furthermore, the content has been expanded by adding novel structural information for peptide entries, including sequences of the previous version. Using a computational methodology developed in the Switch lab, we have generated 3D-models of the putative amyloid fibril cores of WALTZ-DB 2.0 entries. Structural models, coupled with information on the energetic contributions and fibril core stabilities, can be accessed through individual peptide entries. Customized filtering options for subset selections and new modelling graphical features were added to upgrade online accessibility, providing a user-friendly interface for browsing, downloading and updating. WALTZ-DB 2.0 remains the largest open-access repository for amyloid fibril formation determinants and will continue to enhance the development of new approaches focused on accurate prediction of aggregation prone sequences.

scholarly journals Amyloid fibrils from organic solutions of an amphiphilic dipeptide

2019 ◽  
Vol 55 (59) ◽  
pp. 8556-8559 ◽  
Author(s):  
Jordi Casanovas ◽  
Enric Mayans ◽  
Angélica Díaz ◽  
Ana M. Gil ◽  
Ana I. Jiménez ◽  
...  
Keyword(s):  
Organic Solvents ◽  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
C Terminus ◽  
N Terminus ◽  
Organic Solutions

A diphenylalanine amphiphile blocked at the C-terminus with a fluorenylmethyl ester and stabilized at the N-terminus with a trifluoroacetate forms amyloid fibril networks in organic solvents.

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