scholarly journals Role of Glycation in Amyloid: Effect on the Aggregation Process and Cytotoxicity

10.5772/62995 ◽  
2016 ◽  
Author(s):  
Clara Iannuzzi ◽  
Gaetano Irace ◽  
Ivana Sirangelo
Keyword(s):  
Aggregation Process

Extracellular Calcium And Platelets

1981 ◽  
Author(s):  
P M Taylor ◽  
S Heptinstall
Keyword(s):  
Divalent Cation ◽  
Binding Sites ◽  
Divalent Cations ◽  
Extracellular Calcium ◽  
Time Dependent ◽  
Aggregation Process ◽  
Platelet Surface ◽  
Intracellular Pool ◽  
Continuous Movement

To gain more information on the role of extracellular Ca in platelet behaviour, the movement of 45Ca between plasma and platelets has been studied. Ttoo experimental procedures have been used: platelets were either studied in plasma that contained near-physiological levels of divalent cations or were studied in divalent cation-depleted plasma.There was a continuous movement of Ca from plasma into platelets when the latter were suspended in plasma that contained near-physiological levels of divalent cations. The iptake was linear with time (2.0 to 2.5 ng ion Ca/109 platelets/60 mins) and was faster at 37°C than at 25°C. The amount of Ca taken up by the platelets increased as the extracellular Ca level was increased and was markedly inhibited by Mg. Sr did not affect the uptake. EGTA displaced only a small amount of the Ca that associated with the plater lets which indicated that Ca was taken up into an intracellular pool rather than sinply bound to the platelet surface. The relevance of this movement of Ca into the cells to platelet behaviour has not been established.Studies using platelets suspended in divalent cation- depleted plasma shewed that extracellular Ca was in equilibrium with Ca bound at or near the platelet surface. The binding of Ca was time-dependent but saturable (0.30 to 0.50 ng ion Ca/109 platelets/30 mins), and the majority was readily displaced by EGTA. The amount of Ca bound to the cells increased as the extracellular Ca level was increased but was little affected by an excess of either Mg or Sr. Mare Ca bound to platelets when they were incubated at 25°C than at 37°C. This was because platelets lost their ability to bind Ca when they were incubated at 37°C in divalent cation-depleted plasma. This phenomenon was time-dependent and irreversible and was paralleled by a loss in the ability of the platelets to aggregate. These Ca binding sites would seem to be relevant to the aggregation process.

scholarly journals Role of the porphyrins and demulsifiers in the aggregation process of asphaltenes at water/oil interfaces under desalting conditions: a molecular dynamics study

2020 ◽  
Vol 17 (3) ◽  
pp. 797-810 ◽  
Author(s):  
H. Santos Silva ◽  
A. Alfarra ◽  
G. Vallverdu ◽  
D. Bégué ◽  
B. Bouyssiere ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Aggregation Process

scholarly journals Mechanism of amyloid protein aggregation and the role of inhibitors

2019 ◽  
Vol 91 (2) ◽  
pp. 211-229 ◽  
Author(s):  
Sara Linse
Keyword(s):  
Total Concentration ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Aggregation Process ◽  
Secondary Nucleation ◽  
Toxic Species ◽  
Primary Nucleation ◽  
Effective Inhibition ◽  
Aβ Aggregation

Abstract Inhibition of amyloid β peptide (Aβ) aggregation is an important goal due to the connection of this process with Alzheimer’s disease. Traditionally, inhibitors were developed with an aim to retard the overall macroscopic aggregation. However, recent advances imply that approaches based on mechanistic insights may be more powerful. In such approaches, the microscopic steps underlying the aggregation process are identified, and it is established which of these step(s) lead to neurotoxicity. Inhibitors are then derived to specifically target steps involved in toxicity. The Aβ aggregation process is composed of at minimum three microscopic steps: primary nucleation of monomers only, secondary nucleation of monomers on fibril surface, and elongation of fibrils by monomer addition. The vast majority of toxic species are generated from the secondary nucleation process: this may be a key process to inhibit in order to limit toxicity. Inhibition of primary nucleation, which delays the emergence of toxic species without affecting their total concentration, may also be effective. Inhibition of elongation may instead increase the toxicity over time. Here we briefly review findings regarding secondary nucleation of Aβ, its dominance over primary nucleation, and attempts to derive inhibitors that specifically target secondary nucleation with an aim to limit toxicity.

scholarly journals Understanding the Role of Protein Glycation in the Amyloid Aggregation Process

2021 ◽  
Vol 22 (12) ◽  
pp. 6609
Author(s):  
Ivana Sirangelo ◽  
Clara Iannuzzi
Keyword(s):  
Protein Structure ◽  
Protein Function ◽  
The Body ◽  
Protein Glycation ◽  
Amyloid Formation ◽  
Aggregation Process ◽  
Amyloid Aggregation ◽  
Post Translational Modification

Protein function and flexibility is directly related to the native distribution of its structural elements and any alteration in protein architecture leads to several abnormalities and accumulation of misfolded proteins. This phenomenon is associated with a range of increasingly common human disorders, including Alzheimer and Parkinson diseases, type II diabetes, and a number of systemic amyloidosis characterized by the accumulation of amyloid aggregates both in the extracellular space of tissues and as intracellular deposits. Post-translational modifications are known to have an active role in the in vivo amyloid aggregation as able to affect protein structure and dynamics. Among them, a key role seems to be played by non-enzymatic glycation, the most unwanted irreversible modification of the protein structure, which strongly affects long-living proteins throughout the body. This study provided an overview of the molecular effects induced by glycation on the amyloid aggregation process of several protein models associated with misfolding diseases. In particular, we analyzed the role of glycation on protein folding, kinetics of amyloid formation, and amyloid cytotoxicity in order to shed light on the role of this post-translational modification in the in vivo amyloid aggregation process.

scholarly journals Role of the Metal Center in the Modulation of the Aggregation Process of Amyloid Model Systems by Square Planar Complexes Bearing 2-(2'-pyridyl)benzimidazole Ligands

2019 ◽  
Vol 12 (4) ◽  
pp. 154 ◽  
Author(s):  
Florio ◽  
Iacobucci ◽  
Ferraro ◽  
Mansour ◽  
Morelli ◽  
...  
Keyword(s):  
Metal Center ◽  
Model Systems ◽  
Ionization Mass ◽  
Aggregation Process ◽  
Binding Assays ◽  
Metal Compounds ◽  
Aggregation Propensity ◽  
Square Planar ◽  
Square Planar Complexes

The effect of analogue Pd(II)-, Pt(II)-, and Au(III) compounds featuring 2-(2’-pyridyl)benzimidazole on the aggregation propensity of amyloid-like peptides derived from Aβ and from the C-terminal domain of nucleophosmin 1 was investigated. Kinetic profiles of aggregation were evaluated using thioflavin binding assays, whereas the interactions of the compounds with the peptides were studied by UV-Vis absorption spectroscopy and electrospray ionization mass spectrometry. The results indicate that the compounds modulate the aggregation of the investigated peptides using different mechanisms, suggesting that the reactivity of the metal center and the physicochemical properties of the metals (rather than those of the ligands and the geometry of the metal compounds) play a crucial role in determining the anti-aggregation properties.

scholarly journals The chaperone HSPB1 prepares protein aggregates for resolubilization by HSP70

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Conrado C. Gonçalves ◽  
Itai Sharon ◽  
T. Martin Schmeing ◽  
Carlos H. I. Ramos ◽  
Jason C. Young
Keyword(s):  
Lactate Dehydrogenase ◽  
Heat Shock ◽  
Small Heat Shock Protein ◽  
Firefly Luciferase ◽  
Aggregation Process ◽  
Protein Substrates ◽  
Unfolded Protein ◽  
Hsp70 Chaperone ◽  
Chaperone Network

AbstractIn human cells under stress conditions, misfolded polypeptides can form potentially cytotoxic insoluble aggregates. To eliminate aggregates, the HSP70 chaperone machinery extracts and resolubilizes polypeptides for triage to refolding or degradation. Yeast and bacterial chaperones of the small heat-shock protein (sHSP) family can bind substrates at early stages of misfolding, during the aggregation process. The co-aggregated sHSPs then facilitate downstream disaggregation by HSP70. Because it is unknown whether a human sHSP has this activity, we investigated the disaggregation role of human HSPB1. HSPB1 co-aggregated with unfolded protein substrates, firefly luciferase and mammalian lactate dehydrogenase. The co-aggregates formed with HSPB1 were smaller and more regularly shaped than those formed in its absence. Importantly, co-aggregation promoted the efficient disaggregation and refolding of the substrates, led by HSP70. HSPB1 itself was also extracted during disaggregation, and its homo-oligomerization ability was not required. Therefore, we propose that a human sHSP is an integral part of the chaperone network for protein disaggregation.

scholarly journals Privacy-Preserving IoT Data Aggregation Based on Blockchain and Homomorphic Encryption

Sensors ◽  
2021 ◽  
Vol 21 (7) ◽  
pp. 2452
Author(s):  
Faiza Loukil ◽  
Chirine Ghedira-Guegan ◽  
Khouloud Boukadi ◽  
Aïcha-Nabila Benharkat
Keyword(s):  
Data Aggregation ◽  
Homomorphic Encryption ◽  
Privacy Preserving ◽  
Security And Privacy ◽  
Sensitive Information ◽  
Aggregation Process ◽  
Smart Contract ◽  
Reasonable Choice ◽  
Iot Devices

Data analytics based on the produced data from the Internet of Things (IoT) devices is expected to improve the individuals’ quality of life. However, ensuring security and privacy in the IoT data aggregation process is a non-trivial task. Generally, the IoT data aggregation process is based on centralized servers. Yet, in the case of distributed approaches, it is difficult to coordinate several untrustworthy parties. Fortunately, the blockchain may provide decentralization while overcoming the trust problem. Consequently, blockchain-based IoT data aggregation may become a reasonable choice for the design of a privacy-preserving system. To this end, we propose PrivDA, a Privacy-preserving IoT Data Aggregation scheme based on the blockchain and homomorphic encryption technologies. In the proposed system, each data consumer can create a smart contract and publish both terms of service and requested IoT data. Thus, the smart contract puts together into one group potential data producers that can answer the consumer’s request and chooses one aggregator, the role of which is to compute the group requested result using homomorphic computations. Therefore, group-level aggregation obfuscates IoT data, which complicates sensitive information inference from a single IoT device. Finally, we deploy the proposal on a private Ethereum blockchain and give the performance evaluation.

scholarly journals INFLUENCE OF VELOCITY GRADIENT ON OPTIMISATION OF THE AGGREGATION PROCESS AND PHYSICAL PROPERTIES OF FORMED AGGREGATES: Part 1. Inline high density suspension (IHDS) aggregation process

2011 ◽  
Vol 59 (2) ◽  
pp. 107-117 ◽  
Author(s):  
Pavel Polášek
Keyword(s):  
Physical Properties ◽  
Velocity Gradient ◽  
Vital Role ◽  
High Density ◽  
Mean Square ◽  
Aggregation Process ◽  
Root Mean Square Velocity ◽  
Single Root ◽  
Agitation Intensity

INFLUENCE OF VELOCITY GRADIENT ON OPTIMISATION OF THE AGGREGATION PROCESS AND PHYSICAL PROPERTIES OF FORMED AGGREGATES: Part 1. Inline high density suspension (IHDS) aggregation processThis paper deals with optimisation and acceleration of the clarification process. It was established that both these objectives are closely inter-related and can be accomplished by the formation of aggregates with a high agitation intensity until the flocculation optimum is reached. This is a new method of formation of aggregates which is called the Inline High Density Suspension (IHDS) formation process. Further, under the IHDS process the aggregates are formed with a single root-mean-square velocity gradientG>> 50 s-1. It was also established that the process of formation of aggregates (expressed by residual e of the observed determinant) passes through a minimum. This minimum is considered to be the flocculation optimum. Furthermore, the agitation intensity (G) was found to be the inherent means influencing compactness and thereby density of the aggregates formed. This proves the vital role of agitation intensity on the morphological and physical properties of aggregates formed. The resultant aggregates formed by the IHDS process are very compact, dense and homogeneous in their size, shape, volume and inner structure. Last but not least, the IHDS process applied to the HR-CSAV type sludge blanket clarifier facilitated its high attainable upflow velocity above of 25 m h-1.

scholarly journals Fragmentation as an aggregation process: the role of defects

2016 ◽  
Vol 472 (2185) ◽  
pp. 20150679 ◽  
Author(s):  
A. Vledouts ◽  
N. Vandenberghe ◽  
E. Villermaux
Keyword(s):  
Aggregation Process ◽  
Cohesion Strength ◽  
One Dimensional ◽  
Hydrogel Beads ◽  
Capillary Bridges ◽  
Strong Deformation

A cohesive object will eventually break into fragment when experiencing a strong deformation, during an impact for instance. Using necklaces of cohesive magnetized spheres suddenly expanded, we have shown that the fragmentation of this one-dimensional material results from an inverse aggregation cascade (Vledouts et al. 2015 Proc. R. Soc. A 471, 20150678. (doi:10.1098/rspa.2015.0678)). Here, we explore a variant of this process by changing the force law between the attracting spheres, using hydrogel beads linked by capillary bridges. We also investigate the role of (weak) defects in the cohesion strength and the consequences of a distribution of forces between the beads. It is found that fragment do form by a cascade of aggregations, which is interrupted earlier when the force disorder is stronger.

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