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Special Issue "Amyloid Fibrils and Methods for Their Study"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biophysics".

Deadline for manuscript submissions: closed (10 March 2019).

Special Issue Editors

Prof. Dr. Konstantin K. Turoverov
E-Mail Website
Guest Editor
Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Ave., St. Petersburg 194064, Russia
Interests: protein structure, conformation and dynamics; globule and intrinsically disordered proteins; macromolecular crowding; membraneless organelles; protein aggregates; amyloid fibrils formation and structure; biosensors; biomarkers on the basis of fluorescent proteins and phytochromes; photophysics of fluorescent dyes; molecular rotors; intrinsic fluorescence of proteins; spectrofluorimetry device development
Special Issues and Collections in MDPI journals
Dr. Irina M. Kuznetsova
E-Mail Website
Guest Editor
Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Ave., St. Petersburg 194064, Russia
Interests: amyloid fibrils; thioflafin T fluorescence; equilibrium microdialysis; globule and intrinsically disordered proteins; proteins aggregattion; macromolecular crowding; membraneless organelles
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Amyloid fibrils are regular, β-sheet-enriched, long, nanoscale aggregates of proteins with b-strands running perpendicular to the long axis of the fibril. Amyloid fibrils were first found in the tissue of patients suffering from neurodegenerative diseases. Amyloidosis is a great problem of medicine because a number of human diseases (including Alzheimer’s disease, Parkinson’s disease, transmissible spongiform encephalopathies, dialysis amyloidosis, etc.) are characterized by intracellular inclusions or extracellular deposits of proteins in the form of amyloid fibrils.

It is now clear that amyloid fibrils concern many other aspects. The formation of amyloid-like fibrils frequently accompanies over-expression of the recombinant proteins, thus hampering the technology process. However, due to unique architectures and exceptional properties (e.g., high mechanical strength), amyloid fibrils appeared an attractive subject in materials science and nanobiotechnology. Furthermore, the investigations of the structure of amyloid fibrils and the molecular mechanisms of their formation are important for the basic problem of protein folding, because it was found that not only proteins associated with the diseases, but practically all (or most) proteins are prone to form amyloid fibrils in appropriate conditions. Consequently, the ability to fibrillate is a generic property of a polypeptide chain, and the amyloid fibril is a unique state of proteins. However, the formation of amyloid fibrils is most likely by intrinsically disordered proteins (IDPs), because their disordered regions which are important for the ability to interact with their partners are also responsible for a great danger of their aggregation and the formation of amyloid fibrils.

A new era in the study of amyloid fibrils began several years ago, when close attention was paid to membraneless organelles which, according to modern ideas, play the dominant role in the organization of the cellular space. It was shown that IDPs are the main component of all membraneless organelles, and that the abnormal functioning of the membraneless organelles is often accompanied by the formation of amyloid fibrils. Thus, for the first time, the possibility of finding out where and under what circumstances amyloid fibrils are formed in a living cell is opened. It is obvious that the most significant and exciting discoveries in this area are yet to come.

The aim of this Special Issue "Amyloid Fibrils and Methods for Their Study" is to collect under one cover the most important aspects of amyloid fibrils which are currently known—the results of current research and plans for further investigations, as well as new methods for their study development. Experimental papers, up-to-date review articles, and commentaries are all welcomed.

Prof. Dr. Konstantin K. Turoverov
Dr. Irina M. Kuznetsova
Guest Editors

Manuscript Submission Information

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Keywords

  • amyloid fibrils formation and structure
  • protein structure
  • intrinsically disordered proteins
  • protein aggregates
  • macromolecular crowding
  • membraneless organelles

Published Papers (12 papers)

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Research

Jump to: Review

Open AccessArticle
Different Dynamics in 6aJL2 Proteins Associated with AL Amyloidosis, a Conformational Disease
Int. J. Mol. Sci. 2019, 20(17), 4078; https://doi.org/10.3390/ijms20174078 - 21 Aug 2019
Abstract
Light-chain amyloidosis (AL) is the most common systemic amyloidosis and is caused by the deposition of mainly insoluble immunoglobulin light chain amyloid fibrils in multiple organs, causing organ failure and eventually death. The germ-line λ6a has been implicated in AL, where a single [...] Read more.
Light-chain amyloidosis (AL) is the most common systemic amyloidosis and is caused by the deposition of mainly insoluble immunoglobulin light chain amyloid fibrils in multiple organs, causing organ failure and eventually death. The germ-line λ6a has been implicated in AL, where a single point mutant at amino acid 24 (6aJL2-R24G) has been observed in around 25% of patient samples. Structural analysis has shown only subtle differences between both proteins; nevertheless, 6aJL2-R24G is more prone to form amyloid fibrils. To improve our understanding of the role of protein flexibility in amyloid fibril formation, we have used a combination of solution nuclear magnetic resonance spectroscopy and molecular dynamics simulations to complement the structural insight with dynamic knowledge. Fast timescale dynamics (ps–ns) were equivalent for both proteins, but suggested exchange events for some residues. Even though most of the intermediate dynamics (μs–ms) occurred at a similar region for both proteins, the specific characteristics are very different. A minor population detected in the dispersion experiments could be associated with the formation of an off-pathway intermediate that protects from fiber formation more efficiently in the germ-line protein. Moreover, we found that the hydrogen bond patterns for both proteins are similar, but the lifetime for the mutant is significantly reduced; as a consequence, there is a decrease in the stability of the tertiary structure that extends throughout the protein and leads to an increase in the propensity to form amyloid fibers. Full article
(This article belongs to the Special Issue Amyloid Fibrils and Methods for Their Study)
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Open AccessArticle
Distinct Binding Dynamics, Sites and Interactions of Fullerene and Fullerenols with Amyloid-β Peptides Revealed by Molecular Dynamics Simulations
Int. J. Mol. Sci. 2019, 20(8), 2048; https://doi.org/10.3390/ijms20082048 - 25 Apr 2019
Cited by 4
Abstract
The pathology Alzheimer’s disease (AD) is associated with the self-assembly of amyloid-β (Aβ) peptides into β-sheet enriched fibrillar aggregates. A promising treatment strategy is focused on the inhibition of amyloid fibrillization of Aβ peptide. Fullerene C60 is proved to effectively inhibit Aβ [...] Read more.
The pathology Alzheimer’s disease (AD) is associated with the self-assembly of amyloid-β (Aβ) peptides into β-sheet enriched fibrillar aggregates. A promising treatment strategy is focused on the inhibition of amyloid fibrillization of Aβ peptide. Fullerene C60 is proved to effectively inhibit Aβ fibrillation while the poor water-solubility restricts its use as a biomedicine agent. In this work, we examined the interaction of fullerene C60 and water-soluble fullerenol C60(OH)6/C60(OH)12 (C60 carrying 6/12 hydroxyl groups) with preformed Aβ40/42 protofibrils by multiple molecular dynamics simulations. We found that when binding to the Aβ42 protofibril, C60, C60(OH)6 and C60(OH)12 exhibit distinct binding dynamics, binding sites and peptide interaction. The increased number of hydroxyl groups C60 carries leads to slower binding dynamics and weaker binding strength. Binding free energy analysis demonstrates that the C60/C60(OH)6 molecule primarily binds to the C-terminal residues 31–41, whereas C60(OH)12 favors to bind to N-terminal residues 4–14. The hydrophobic interaction plays a critical role in the interplay between Aβ and all the three nanoparticles, and the π-stacking interaction gets weakened as C60 carries more hydroxyls. In addition, the C60(OH)6 molecule has high affinity to form hydrogen bonds with protein backbones. The binding behaviors of C60/C60(OH)6/C60(OH)12 to the Aβ40 protofibril resemble with those to Aβ42. Our work provides a detailed picture of fullerene/fullerenols binding to Aβ protofibril, and is helpful to understand the underlying inhibitory mechanism. Full article
(This article belongs to the Special Issue Amyloid Fibrils and Methods for Their Study)
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Open AccessArticle
Tannic Acid-Induced Surface-Catalyzed Secondary Nucleation during the Amyloid Fibrillation of Hen Egg-White Lysozyme
Int. J. Mol. Sci. 2018, 19(12), 4009; https://doi.org/10.3390/ijms19124009 - 12 Dec 2018
Cited by 1
Abstract
Amyloid fibrillation by hen egg white lysozyme under the influence of tannic acid was investigated by atomic force microscopy and fluorescence spectroscopy. Tannic acid was found to be able to induce the formation of amyloid fibrils with an interesting mixed morphology. Such morphology [...] Read more.
Amyloid fibrillation by hen egg white lysozyme under the influence of tannic acid was investigated by atomic force microscopy and fluorescence spectroscopy. Tannic acid was found to be able to induce the formation of amyloid fibrils with an interesting mixed morphology. Such morphology features with the existence of areas of thickening alternating with areas of normal height. This novel modulation effect of tannic acid on amyloid fibrillation was interpreted by the established surface-catalyzed secondary nucleation theory. We further performed a fluorescence quenching study to investigate the intermolecular interaction between tannic acid and lysozyme. The results support that lysozyme and tannic acid interact with each other mainly through hydrophobic interactions. We also discussed why hydrogen-bonding interaction is not a dominant factor in the interaction between tannic acid and lysozyme though tannic acid contains a significant amount of hydroxyl groups. Our work provides new insight into the effect of tannic acid, a well-known amyloid inhibitor, on amyloid fibrillation. Full article
(This article belongs to the Special Issue Amyloid Fibrils and Methods for Their Study)
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Open AccessArticle
The Pub1 and Upf1 Proteins Act in Concert to Protect Yeast from Toxicity of the [PSI+] Prion
Int. J. Mol. Sci. 2018, 19(11), 3663; https://doi.org/10.3390/ijms19113663 - 20 Nov 2018
Cited by 1
Abstract
The [PSI+] nonsense-suppressor determinant of Saccharomyces cerevisiae is based on the formation of heritable amyloids of the Sup35 (eRF3) translation termination factor. [PSI+] amyloids have variants differing in amyloid structure and in the strength of the suppressor [...] Read more.
The [PSI+] nonsense-suppressor determinant of Saccharomyces cerevisiae is based on the formation of heritable amyloids of the Sup35 (eRF3) translation termination factor. [PSI+] amyloids have variants differing in amyloid structure and in the strength of the suppressor phenotype. The appearance of [PSI+], its propagation and manifestation depend primarily on chaperones. Besides chaperones, the Upf1/2/3, Siw14 and Arg82 proteins restrict [PSI+] formation, while Sla2 can prevent [PSI+] toxicity. Here, we identify two more non-chaperone proteins involved in [PSI+] detoxification. We show that simultaneous lack of the Pub1 and Upf1 proteins is lethal to cells harboring [PSI+] variants with a strong, but not with a weak, suppressor phenotype. This lethality is caused by excessive depletion of the Sup45 (eRF1) termination factor due to its sequestration into Sup35 polymers. We also show that Pub1 acts to restrict excessive Sup35 prion polymerization, while Upf1 interferes with Sup45 binding to Sup35 polymers. These data allow consideration of the Pub1 and Upf1 proteins as a novel [PSI+] detoxification system. Full article
(This article belongs to the Special Issue Amyloid Fibrils and Methods for Their Study)
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Open AccessArticle
Structural Features of Amyloid Fibrils Formed from the Full-Length and Truncated Forms of Beta-2-Microglobulin Probed by Fluorescent Dye Thioflavin T
Int. J. Mol. Sci. 2018, 19(9), 2762; https://doi.org/10.3390/ijms19092762 - 14 Sep 2018
Cited by 2
Abstract
The persistence of high concentrations of beta-2-microglobulin (β2M) in the blood of patients with acute renal failure leads to the development of the dialysis-related amyloidosis. This disease manifests in the deposition of amyloid fibrils formed from the various forms of β2M in the [...] Read more.
The persistence of high concentrations of beta-2-microglobulin (β2M) in the blood of patients with acute renal failure leads to the development of the dialysis-related amyloidosis. This disease manifests in the deposition of amyloid fibrils formed from the various forms of β2M in the tissues and biological fluids of patients. In this paper, the amyloid fibrils formed from the full-length β2M (β2m) and its variants that lack the 6 and 10 N-terminal amino acids of the protein polypeptide chain (ΔN6β2m and ΔN10β2m, respectively) were probed by using the fluorescent dye thioflavin T (ThT). For this aim, the tested solutions were prepared via the equilibrium microdialysis approach. Spectroscopic analysis of the obtained samples allowed us to detect one binding mode (type) of ThT interaction with all the studied variants of β2M amyloid fibrils with affinity ~104 M−1. This interaction can be explained by the dye molecules incorporation into the grooves that were formed by the amino acids side chains of amyloid protofibrils along the long axis of the fibrils. The decrease in the affinity and stoichiometry of the dye interaction with β2M fibrils, as well as in the fluorescence quantum yield and lifetime of the bound dye upon the shortening of the protein amino acid sequence were shown. The observed differences in the ThT-β2M fibrils binding parameters and characteristics of the bound dye allowed to prove not only the difference of the ΔN10β2m fibrils from other β2M fibrils (that can be detected visually, for example, by transmission electron microscopy (TEM), but also the differences between β2m and ΔN6β2m fibrils (that can not be unequivocally confirmed by other approaches). These results prove an essential role of N-terminal amino acids of the protein in the formation of the β2M amyloid fibrils. Information about amyloidogenic protein sequences can be claimed in the development of ways to inhibit β2M fibrillogenesis for the treatment of dialysis-related amyloidosis. Full article
(This article belongs to the Special Issue Amyloid Fibrils and Methods for Their Study)
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Open AccessArticle
Investigation of α-Synuclein Amyloid Fibrils Using the Fluorescent Probe Thioflavin T
Int. J. Mol. Sci. 2018, 19(9), 2486; https://doi.org/10.3390/ijms19092486 - 23 Aug 2018
Cited by 10
Abstract
In this work, α-synuclein amyloid fibrils—the formation of which is a biomarker of Parkinson’s disease—were investigated using the fluorescent probe thioflavin T (ThT). The experimental conditions of protein fibrillogenesis were chosen so that a sufficient number of continuous measurements could be performed to [...] Read more.
In this work, α-synuclein amyloid fibrils—the formation of which is a biomarker of Parkinson’s disease—were investigated using the fluorescent probe thioflavin T (ThT). The experimental conditions of protein fibrillogenesis were chosen so that a sufficient number of continuous measurements could be performed to characterize and analyze all stages of this process. The reproducibility of fibrillogenesis and the structure of the obtained aggregates (which is a critical point for further investigation) were proven using a wide range of physical-chemical methods. For the determination of ThT-α-synuclein amyloid fibril binding parameters, the sample and reference solutions were prepared using equilibrium microdialysis. By utilizing absorption spectroscopy of these solutions, the ThT-fibrils binding mode with a binding constant of about 104 M−1 and stoichiometry of ThT per protein molecule of about 1:8 was observed. Fluorescence spectroscopy of the same solutions with the subsequent correction of the recorded fluorescence intensity on the primary inner filter effect allowed us to determine another mode of ThT binding to fibrils, with a binding constant of about 106 M−1 and stoichiometry of about 1:2500. Analysis of the photophysical characteristics of the dye molecules bound to the sites of different binding modes allowed us to assume the possible localization of these sites. The obtained differences in the ThT binding parameters to the amyloid fibrils formed from α-synuclein and other amyloidogenic proteins, as well as in the photophysical characteristics of the bound dye, confirmed the hypothesis of amyloid fibril polymorphism. Full article
(This article belongs to the Special Issue Amyloid Fibrils and Methods for Their Study)
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Open AccessArticle
Assembly Mechanism for Aggregation of Amyloid Fibrils
Int. J. Mol. Sci. 2018, 19(7), 2141; https://doi.org/10.3390/ijms19072141 - 23 Jul 2018
Cited by 1
Abstract
The assembly mechanism for aggregation of amyloid fibril is important and fundamental for any quantitative and physical descriptions because it needs to have a deep understanding of both molecular and statistical physics. A theoretical model with three states including coil, helix and sheet [...] Read more.
The assembly mechanism for aggregation of amyloid fibril is important and fundamental for any quantitative and physical descriptions because it needs to have a deep understanding of both molecular and statistical physics. A theoretical model with three states including coil, helix and sheet is presented to describe the amyloid formation. The corresponding general mathematical expression of N molecule systems are derived, including the partition function and thermodynamic quantities. We study the equilibrium properties of the system in the solution and find that three molecules have the extreme value of free energy. The denaturant effect on molecular assemble is also discussed. Furthermore, we apply the kinetic theories to take account of the nucleation and growth of the amyloid in the solution. It has been shown that our theoretical results can be compared with experimental results. Full article
(This article belongs to the Special Issue Amyloid Fibrils and Methods for Their Study)
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Open AccessArticle
MK-0677, a Ghrelin Agonist, Alleviates Amyloid Beta-Related Pathology in 5XFAD Mice, an Animal Model of Alzheimer’s Disease
Int. J. Mol. Sci. 2018, 19(6), 1800; https://doi.org/10.3390/ijms19061800 - 18 Jun 2018
Cited by 7
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive deficits, neuroinflammation, and neuronal death. The primary pathogenic cause is believed to be the accumulation of pathogenic amyloid beta (Aβ) assemblies in the brain. Ghrelin, which is a peptide hormone predominantly secreted [...] Read more.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive deficits, neuroinflammation, and neuronal death. The primary pathogenic cause is believed to be the accumulation of pathogenic amyloid beta (Aβ) assemblies in the brain. Ghrelin, which is a peptide hormone predominantly secreted from the stomach, is an endogenous ligand for the growth hormone secretagogue-receptor type 1a (GHS-R1a). MK-0677 is a ghrelin agonist that potently stimulates the GHS-R1a ghrelin receptor. Interestingly, previous studies have shown that ghrelin improves cognitive impairments and attenuates neuronal death and neuroinflammation in several neurological disorders. However, it is unknown whether MK-0677 can affect Aβ accumulation or Aβ-mediated pathology in the brains of patients with AD. Therefore, we examined the effects of MK-0677 administration on AD-related pathology in 5XFAD mice, an Aβ-overexpressing transgenic mouse model of AD. MK-0677 was intraperitoneally administered to three-month-old 5XFAD mice. To visualize Aβ accumulation, neuroinflammation, and neurodegeneration, thioflavin-S staining and immunostaining with antibodies against Aβ (4G8), ionized calcium-binding adaptor molecule 1 (Iba-1), glial fibrillary acidic protein (GFAP), neuronal nuclear antigen (NeuN), and synaptophysin were conducted in the neocortex of 5XFAD and wild-type mice, and to evaluate changes of phosphorylated cyclic adenosine monophosphate (cAMP) response element binding protein (pCREB) levels, immunostaining with antibody against pCREB was performed in dentate gyrus of the hippocampus of 5XFAD and wild-type mice. The histological analyses indicated that MK-0677-treated 5XFAD mice showed reduced Aβ deposition, gliosis, and neuronal and synaptic loss in the deep cortical layers, and inhibited the decrement of pCREB levels in dentate gyrus of the hippocampus compared to vehicle-treated 5XFAD mice. Our results showed that activation of the ghrelin receptor with MK-0677 inhibited the Aβ burden, neuroinflammation, and neurodegeneration, which suggested that MK-0677 might have potential as a treatment of the early phase of AD. Full article
(This article belongs to the Special Issue Amyloid Fibrils and Methods for Their Study)
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Review

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Open AccessReview
Novel Therapeutic Potentials of Taxifolin for Amyloid-β-associated Neurodegenerative Diseases and Other Diseases: Recent Advances and Future Perspectives
Int. J. Mol. Sci. 2019, 20(9), 2139; https://doi.org/10.3390/ijms20092139 - 30 Apr 2019
Cited by 4
Abstract
Amyloid-β (Aβ) has been closely implicated in the pathogenesis of cerebral amyloid angiopathy (CAA) and Alzheimer’s disease (AD), the major causes of dementia. Thus, Aβ could be a target for the treatment of these diseases, for which, currently, there are no established effective [...] Read more.
Amyloid-β (Aβ) has been closely implicated in the pathogenesis of cerebral amyloid angiopathy (CAA) and Alzheimer’s disease (AD), the major causes of dementia. Thus, Aβ could be a target for the treatment of these diseases, for which, currently, there are no established effective treatments. Taxifolin is a bioactive catechol-type flavonoid present in various plants, such as herbs, and it exhibits pleiotropic effects including anti-oxidant and anti-glycation activities. Recently, we have demonstrated that taxifolin inhibits Aβ fibril formation in vitro and have further shown that it improves cerebral blood flow, facilitating Aβ clearance in the brain and suppressing cognitive decline in a mouse model of CAA. These findings suggest the novel therapeutic potentials of taxifolin for CAA. Furthermore, recent extensive studies have reported several novel aspects of taxifolin supporting its potential as a therapeutic drug for AD and metabolic diseases with a high risk for dementia as well as for CAA. In this review, we have summarized the recent advances in taxifolin research based on in vitro, in vivo, and in silico approaches. Furthermore, we have discussed future research directions on the potential of taxifolin for use in novel therapeutic strategies for CAA, AD, and metabolic diseases with an increased risk for dementia. Full article
(This article belongs to the Special Issue Amyloid Fibrils and Methods for Their Study)
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Open AccessReview
Implications of Metal Binding and Asparagine Deamidation for Amyloid Formation
Int. J. Mol. Sci. 2018, 19(8), 2449; https://doi.org/10.3390/ijms19082449 - 19 Aug 2018
Cited by 2
Abstract
Increasing evidence suggests that amyloid formation, i.e., self-assembly of proteins and the resulting conformational changes, is linked with the pathogenesis of various neurodegenerative disorders such as Alzheimer’s disease, prion diseases, and Lewy body diseases. Among the factors that accelerate or inhibit oligomerization, we [...] Read more.
Increasing evidence suggests that amyloid formation, i.e., self-assembly of proteins and the resulting conformational changes, is linked with the pathogenesis of various neurodegenerative disorders such as Alzheimer’s disease, prion diseases, and Lewy body diseases. Among the factors that accelerate or inhibit oligomerization, we focus here on two non-genetic and common characteristics of many amyloidogenic proteins: metal binding and asparagine deamidation. Both reflect the aging process and occur in most amyloidogenic proteins. All of the amyloidogenic proteins, such as Alzheimer’s β-amyloid protein, prion protein, and α-synuclein, are metal-binding proteins and are involved in the regulation of metal homeostasis. It is widely accepted that these proteins are susceptible to non-enzymatic posttranslational modifications, and many asparagine residues of these proteins are deamidated. Moreover, these two factors can combine because asparagine residues can bind metals. We review the current understanding of these two common properties and their implications in the pathogenesis of these neurodegenerative diseases. Full article
(This article belongs to the Special Issue Amyloid Fibrils and Methods for Their Study)
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Open AccessReview
Recent Advances by In Silico and In Vitro Studies of Amyloid-β 1-42 Fibril Depicted a S-Shape Conformation
Int. J. Mol. Sci. 2018, 19(8), 2415; https://doi.org/10.3390/ijms19082415 - 16 Aug 2018
Cited by 8
Abstract
The amyloid-β 1-42 (Aβ1-42) peptide is produced by proteolytic cleavage of the amyloid precursor protein (APP) by sequential reactions that are catalyzed by γ and β secretases. Aβ1-42, together with the Tau protein are two principal hallmarks of Alzheimer’s disease (AD) that are [...] Read more.
The amyloid-β 1-42 (Aβ1-42) peptide is produced by proteolytic cleavage of the amyloid precursor protein (APP) by sequential reactions that are catalyzed by γ and β secretases. Aβ1-42, together with the Tau protein are two principal hallmarks of Alzheimer’s disease (AD) that are related to disease genesis and progression. Aβ1-42 possesses a higher aggregation propensity, and it is able to form fibrils via nucleated fibril formation. To date, there are compounds available that prevent Aβ1-42 aggregation, but none have been successful in clinical trials, possibly because the Aβ1-42 structure and aggregation mechanisms are not thoroughly understood. New molecules have been designed, employing knowledge of the Aβ1-42 structure and are based on preventing or breaking the ionic interactions that have been proposed for formation of the Aβ1-42 fibril U-shaped structure. Recently, a new Aβ1-42 fibril S-shaped structure was reported that, together with its aggregation and catalytic properties, could be helpful in the design of new inhibitor molecules. Therefore, in silico and in vitro methods have been employed to analyze the Aβ1-42 fibril S-shaped structure and its aggregation to obtain more accurate Aβ1-42 oligomerization data for the design and evaluation of new molecules that can prevent the fibrillation process. Full article
(This article belongs to the Special Issue Amyloid Fibrils and Methods for Their Study)
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Open AccessReview
Protein Co-Aggregation Related to Amyloids: Methods of Investigation, Diversity, and Classification
Int. J. Mol. Sci. 2018, 19(8), 2292; https://doi.org/10.3390/ijms19082292 - 04 Aug 2018
Cited by 2
Abstract
Amyloids are unbranched protein fibrils with a characteristic spatial structure. Although the amyloids were first described as protein deposits that are associated with the diseases, today it is becoming clear that these protein fibrils play multiple biological roles that are essential for different [...] Read more.
Amyloids are unbranched protein fibrils with a characteristic spatial structure. Although the amyloids were first described as protein deposits that are associated with the diseases, today it is becoming clear that these protein fibrils play multiple biological roles that are essential for different organisms, from archaea and bacteria to humans. The appearance of amyloid, first of all, causes changes in the intracellular quantity of the corresponding soluble protein(s), and at the same time the aggregate can include other proteins due to different molecular mechanisms. The co-aggregation may have different consequences even though usually this process leads to the depletion of a functional protein that may be associated with different diseases. The protein co-aggregation that is related to functional amyloids may mediate important biological processes and change of protein functions. In this review, we survey the known examples of the amyloid-related co-aggregation of proteins, discuss their pathogenic and functional roles, and analyze methods of their studies from bacteria and yeast to mammals. Such analysis allow for us to propose the following co-aggregation classes: (i) titration: deposition of soluble proteins on the amyloids formed by their functional partners, with such interactions mediated by a specific binding site; (ii) sequestration: interaction of amyloids with certain proteins lacking a specific binding site; (iii) axial co-aggregation of different proteins within the same amyloid fibril; and, (iv) lateral co-aggregation of amyloid fibrils, each formed by different proteins. Full article
(This article belongs to the Special Issue Amyloid Fibrils and Methods for Their Study)
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