Interaction Volume Is a Measure of the Aggregation Propensity of Amyloid-β

2020 ◽  
Vol 11 (10) ◽  
pp. 3993-4000
Author(s):  
Leena Aggarwal ◽  
Parbati Biswas
Keyword(s):  
Amyloid Β ◽  
Interaction Volume ◽  
Aggregation Propensity

pH changes the aggregation propensity of amyloid-β without altering the monomer conformation

2014 ◽  
Vol 16 (3) ◽  
pp. 885-889 ◽  
Author(s):  
Debanjan Bhowmik ◽  
Christina M. MacLaughlin ◽  
Muralidharan Chandrakesan ◽  
Prashanth Ramesh ◽  
Ravindra Venkatramani ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Ph Changes ◽  
Aggregation Propensity

Glycation induces conformational changes in the amyloid-β peptide and enhances its aggregation propensity: molecular insights

2016 ◽  
Vol 18 (46) ◽  
pp. 31446-31458 ◽  
Author(s):  
Asis K. Jana ◽  
Kedar B. Batkulwar ◽  
Mahesh J. Kulkarni ◽  
Neelanjana Sengupta
Keyword(s):  
Conformational Changes ◽  
In Silico ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Advanced Glycation ◽  
Aggregation Propensity

Underlying molecular insights into the higher aggregation propensity of the advanced glycation modified Aβ (or AGE-Aβ) from synchronizedin vitroandin silicostudies.

scholarly journals Amyloid fibrils prepared using an acetylated and methyl amidated peptide model of the α-Synuclein NAC 71–82 amino acid stretch contain an additional cross-β structure also found in prion proteins

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Thomas Näsström ◽  
Per Ola Andersson ◽  
Christian Lejon ◽  
Björn C. G. Karlsson
Keyword(s):  
Amino Acid ◽  
Protein Misfolding ◽  
Prion Proteins ◽  
Lewy Bodies ◽  
Amyloid Β ◽  
Full Length ◽  
Aggregation Propensity ◽  
Amino Acid Stretch ◽  
Amidated Peptide ◽  
Β Sheet

Abstract The 71–82 fragment of the non-amyloid-β component (NAC) region of the Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) related protein α-Synuclein, has been reported to be important during protein misfolding. Although reports have demonstrated the importance of this fragment for the aggregation properties of the full-length protein, its exact role in pre-fibrillar oligomerisation, fibrillar growth and morphology has not yet been fully elucidated. Here, we provide evidence that fibrils prepared from an acetylated and methyl amidated peptide of the NAC 71–82 amino acid stretch of α-Synuclein are amyloid and contain, in addition to the cross-β structure detected in the full-length protein fibrils, a cross-β structure previously observed in prion proteins. These results shed light on the aggregation propensity of the NAC 71–82 amino acid stretch of the full-length protein but also the roles of the N- and C-terminal domains of α-Synuclein in balancing this aggregation propensity. The results also suggest that early aggregated forms of the capped NAC 71–82 peptide generated structures were stabilised by an anti-parallel and twisted β-sheet motif. Due to its expected toxicity, this β-sheet motif may be a promising molecular target for the development of therapeutic strategies for PD and DLB.

Modeling the Aggregation Propensity and Toxicity of Amyloid-β Variants

2015 ◽  
Vol 47 (1) ◽  
pp. 215-229 ◽  
Author(s):  
Manish K. Tiwari ◽  
Kasper P. Kepp
Keyword(s):  
Amyloid Β ◽  
Aggregation Propensity

scholarly journals A Capped Peptide of the Aggregation Prone NAC 71–82 Amino Acid Stretch of α-Synuclein Folds into Soluble β-Sheet Oligomers at Low and Elevated Peptide Concentrations

2020 ◽  
Vol 21 (5) ◽  
pp. 1629 ◽  
Author(s):  
Thomas Näsström ◽  
Jörgen Ådén ◽  
Fumina Shibata ◽  
Per Ola Andersson ◽  
Björn C.G. Karlsson
Keyword(s):  
Amino Acid ◽  
Prion Proteins ◽  
Lewy Bodies ◽  
Amyloid Β ◽  
Aggregation Kinetics ◽  
Lewy Neurites ◽  
Aggregation Propensity ◽  
Amino Acid Stretch ◽  
Dynamics Simulations ◽  
Β Sheet

Although Lewy bodies and Lewy neurites are hallmarks of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), misfolded α-synuclein oligomers are nowadays believed to be key for the development of these diseases. Attempts to target soluble misfolded species of the full-length protein have been limited so far, probably due to the fast aggregation kinetics and burial of aggregation prone segments in final cross-β-sheet fibrils. A previous characterisation study of fibrils prepared from a capped peptide of the non-amyloid β-component (NAC) 71–82 amino acid stretch of α-synuclein demonstrated an increased aggregation propensity resulting in a cross-β-structure that is also found in prion proteins. From this, it was suggested that capped NAC 71–82 peptide oligomers would provide interesting motifs with a capacity to regulate disease development. Here, we demonstrated, from a series of circular dichroism spectroscopic measurements and molecular dynamics simulations, the molecular-environment-sensitive behaviour of the capped NAC 71–82 peptide in a solution phase and the formation of β-sheet oligomeric structures in the supernatant of a fibrillisation mixture. These results highlighted the use of the capped NAC 71–82 peptide as a motif in the preparation of oligomeric β-sheet structures that potentially could be used in therapeutic strategies in the fight against progressive neurodegenerative disorders, such as PD and DLB.

scholarly journals Recent Advances by In Silico and In Vitro Studies of Amyloid-β 1-42 Fibril Depicted a S-Shape Conformation

2018 ◽  
Vol 19 (8) ◽  
pp. 2415 ◽  
Author(s):  
Daniel Miguel Ángel Villalobos Acosta ◽  
Brenda Chimal Vega ◽  
José Correa Basurto ◽  
Leticia Guadalupe Fragoso Morales ◽  
Martha Cecilia Rosales Hernández
Keyword(s):  
Clinical Trials ◽  
Amyloid Precursor Protein ◽  
Tau Protein ◽  
In Silico ◽  
Catalytic Properties ◽  
Amyloid Β ◽  
Ionic Interactions ◽  
In Vitro Methods ◽  
Aggregation Propensity

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.

High Resolution Scanning Electron Microscopy

1991 ◽  
Vol 49 ◽  
pp. 478-479
Author(s):  
David Joy ◽  
James Pawley
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Electron Beam ◽  
Electron Microscope ◽  
High Resolution ◽  
Scanning Electron Microscope ◽  
Electron Probe ◽  
Impact Point ◽  
Interaction Volume ◽  
Scanning Electron

The scanning electron microscope (SEM) builds up an image by sampling contiguous sub-volumes near the surface of the specimen. A fine electron beam selectively excites each sub-volume and then the intensity of some resulting signal is measured. The spatial resolution of images made using such a process is limited by at least three factors. Two of these determine the size of the interaction volume: the size of the electron probe and the extent to which detectable signal is excited from locations remote from the beam impact point. A third limitation emerges from the fact that the probing beam is composed of a finite number of discrete particles and therefore that the accuracy with which any detectable signal can be measured is limited by Poisson statistics applied to this number (or to the number of events actually detected if this is smaller).

High-resolution topographic SEM and radiation damage: The rationale for using low beam voltage

1992 ◽  
Vol 50 (2) ◽  
pp. 1278-1279
Author(s):  
James Pawley ◽  
David Joy
Keyword(s):  
High Resolution ◽  
Imaging Techniques ◽  
Morphological Structure ◽  
Radiation Sensitivity ◽  
Beam Specimen ◽  
Measured Signal ◽  
Practical Consideration ◽  
Interaction Volume ◽  
Impact Area ◽  
Signal Contrast

The scanning electron microscope (SEM) builds up an image by sampling contiguous sub-volumes near the surface of the specimen. A fine electron beam selectively excites each sub-volume and then the intensity of some resulting signal is measured and then plotted as a corresponding intensity in an image. The spatial resolution of such an image is limited by at least three factors. Two of these determine the size of the interaction volume: the size of the electron probe and the extent to which detectable signal is excited from locations remote from the beam impact area. A third limitation emerges from the fact that the probing beam is composed of a number of discrete particles and therefore that the accuracy with which any detectable signal can be measured is limited by Poisson statistics applied to this number (or to the number of events actually detected if this is smaller). As in all imaging techniques, the limiting signal contrast required to recognize a morphological structure is constrained by this statistical consideration. The only way to overcome this limit is to increase either the contrast of the measured signal or the number of beam/specimen interactions detected. Unfortunately, these interactions deposit ionizing radiation that may damage the very structure under investigation. As a result, any practical consideration of the high resolution performance of the SEM must consider not only the size of the interaction volume but also the contrast available from the signal producing the image and the radiation sensitivity of the specimen.

Low-voltage EDS of magnesium ferrite Dendrites in a FEG-SEM

1996 ◽  
Vol 54 ◽  
pp. 478-479
Author(s):  
Matthew T. Johnson ◽  
Ian M. Anderson ◽  
Jim Bentley ◽  
C. Barry Carter
Keyword(s):  
Monte Carlo ◽  
Quantitative Analysis ◽  
Monte Carlo Simulations ◽  
Cross Section ◽  
Spatial Resolution ◽  
Low Voltage ◽  
Magnesium Ferrite ◽  
X Ray ◽  
Interaction Volume ◽  
Ferrite Spinel

Energy-dispersive X-ray spectrometry (EDS) performed at low (≤ 5 kV) accelerating voltages in the SEM has the potential for providing quantitative microanalytical information with a spatial resolution of ∼100 nm. In the present work, EDS analyses were performed on magnesium ferrite spinel [(MgxFe1−x)Fe2O4] dendrites embedded in a MgO matrix, as shown in Fig. 1. spatial resolution of X-ray microanalysis at conventional accelerating voltages is insufficient for the quantitative analysis of these dendrites, which have widths of the order of a few hundred nanometers, without deconvolution of contributions from the MgO matrix. However, Monte Carlo simulations indicate that the interaction volume for MgFe2O4 is ∼150 nm at 3 kV accelerating voltage and therefore sufficient to analyze the dendrites without matrix contributions.Single-crystal {001}-oriented MgO was reacted with hematite (Fe2O3) powder for 6 h at 1450°C in air and furnace cooled. The specimen was then cleaved to expose a clean cross-section suitable for microanalysis.

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